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Effects of
drugs & chemicals on baby's brain: Psychoteratology
Author
Paul
Kenyon
Visit the SALMON Bookshop for recommended
books on this topic |
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Overview:
 This
lecture addresses an important practical question:
What
safeguards are in place to detect medicines that might harm a baby if
they were taken during pregnancy?
This
is an important issue in the light of the thalidomide tragedy. We begin
by trying to gauge the size of the threat by examining the proportion
of pregnant women that take medicines, and the type of medicines that
are most frequently prescribed in pregnancy.
We
move on to consider critical periods in human in utero development -
this may give insight into which behavioural systems might be affected
by drug ingestion at various stages of gestation.
The
heart of the lecture is a discussion of the tests that are used to
detect behavioural teratogens - chemicals that could compromise a
child's subsequent behavioural development. As psychologists you should
be able to form an opinion on the relative usefulness of these tests.
We consider the evidence that substances taken during pregnancy
interfere with psychosexual differentiation in animal models. This
possibility does not appear to be seriously considered in current tests
of human medicines. You already know quite a lot about the psychosexual
differentiation from your earlier lectures.
I
hope you will begin to appreciate how your theoretical understanding
can be brought to bear on this important issue that concerns everyone -
the health and happiness of the new-born child. Of course you should be
aware of the social, political and economic implications of these
findings.
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Learning
Objectives
After studying the material on this page you should be able to:
- Describe
the scope of psychoteratology
- List
four teratogens
- Recognize
the symptoms of Foetal Alcohol Syndrome
- Explain
why it is difficult to detect the effect(s) of a psychoteratogen in the
general population
- Describe
the general effects of teratogens on the body
- Explain
why the unborn child may be at psychoteratogenic risk
- Recognize
the critical periods for organ development in the embryo and foetus
- Compare
international guidelines for testing drug safety in animals
- Explain
how drug exposure could effect psychosexual differentiation
- Critical
evaluate Anand and Van Thiel's (1982) study of the effects of
cimetidine on male rat sexual behaviour
- Describe
the effects of perinatal stress, alcohol, and dopaminergic drugs on
sexually dimorphic behaviours in animals
- Critically
evaluate the risk to the new-born child of damage caused by chemical
exposure in utero
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What
is psychoteratology?
- Teratology
is derived from the Greek word teratos which
means 'demon' or 'monster'.
- Substances
which cause these effects are known as teratogenic agents or
developmental toxicants.
- Psychoteratology
or Neurobehavioural teratology deals
with the effects of these substances on the development of behaviour.
The Neurobehavioural
Teratology Society
describes neurobehavioural teratology as
"...the study of
functional brain deficits (like learning disorders) that result from
something going wrong
during development. Whether it is a genetic defect that is inherited,
or exposure to some
substance or circumstance during pregnancy, the result can be some form
of functional
birth defect that may occur without an obvious visible sign. It
involves studying those
birth defects related to the development of the brain that may not be
visible to the naked
eye, but are disabling to that person."
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Some
of the known causes of birth defects are:
- alcohol
- hormones
- diseases
- heavy
metals
These
substances are transferred from the mother's blood, across the placenta
into the fetal system, where they cause malformations and defects.
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| Alcohol is a teratogen
and the cause of a pattern of malformations known as Fetal
Alcohol Syndrome (FAS). The syndrome has become the leading
cause of mental retardation arising from the action of known
teratogenic agents. It is characterized by a group of physical and
mental birth defects that are the direct result of drinking alcohol
during pregnancy. This condition continues to represent a substantial
public health problem, as well as an economic burden to society. None
the less, FAS is 100% preventable. This information is adapted from the
Texas
Genetics Network Newsletter that has a very useful article on
FAS |
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Detection
of behavioural teratogens
The
effects of behavioural teratogens
may be very difficult to detect in humans because subtle effects can be
impossible to
detect against a background of significant variation in behaviour
across the population.
Imagine
that a new teratogen has the effect
of reducing each affected child's IQ by five points.
- by
definition IQ is normally distributed in the population with a mean of
100.
- 99.5%
of IQ scores in the population are within the range 55 to 145.
- if
the new teratogen decreased IQ by 5 points, 99.2% of the population
would still have an IQ within the 'normal' range of 55 to 145
- consequently
the effect of the teratogen would be virtually undetectable by
examining the 'normal' population
However
a teratogen that decreased IQ by 5
points in the population would lead to
- a
huge increase in the number of people with mental
retardation and
- a
significant decrease in the number of gifted
people in the population.
However
- because both these groups form such
a small proportion (0.25%) of the normal population - the effect of the
teratogen would
remain undetected in studies of the whole population.
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| Figures
based on Slotkin (1998) |
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Principles
of teratology
Teratologists have discovered the following principles from studies in
animals and humans:
- there
are critical periods during which exposure to a
teratogen affects subsequent behaviour
- species
differ in their susceptibility to teratogens
- teratogens
may affect the development of specific organs
within the body
- The dose
of teratogen to which the developing organism is exposed influences the
outcome
- Toxic
effects can range from:
- death
- at very high doses
- malformation
- growth
retardation
- behavioral
changes - at relatively low doses
Frequency
of taking medicines during pregnancy
The
frequency, number and range of drugs
taken in pregnancy is higher than you might expect. Psychoactive drugs
may have to be
taken in pregnancy; their mode of action involves effects on
neurotransmitters - what is
the effect of this on the developing brain?
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In the 1960's,
thalidomide was used as an anti-nausea agent, causing several thousand
european children to be born with limb and body malformations.
Thalidomide had a major impact on the attitudes of pharmaceutical
companies and governments towards drug safety. Despite the obvious
deformities suffered by these children, it was not immediately obvious
that the drug was responsible because similar deformities can occur in
the absence of exposure to thalidomide. In other words this is not a
completely new condition - it occurs at a certain level in the
population.
This
reinforces the point made earlier that it is difficult to detect teratogens
Despite
the thalimide tragedy, the average number of medicines taken by each
woman during pregnancy rose between 1963 and 1973.
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In
a survey of 156 women carried out in 1971, Nelson & Forfar
found that nearly all women were taking medicines during pregnancy. The
majority of women were also taking self-prescribed medications. The
table below is a comparison of drug useage, average number of drugs
taken per woman, and self medication in Scotland (Nelson &
Forfar, 1971), USA (Heineman et al, 1977, Doering & Stewart,
1978), Belguim (Meire et al, 1979) and the Netherlands (Eskes et al,
1983).
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Scotland
|
USA
|
Belguim
|
Netherlands
|
| % Drug usage
|
97% |
94% |
93% |
99% |
83 to 71% |
| Average number
per woman |
3.5 |
11 |
3.8 |
4.4 |
2.4 to 2.3 |
| Self-medication
|
65% |
|
|
18% |
11 to 7% |
|
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Types
of medicines taken during pregnancy
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This
figure shows the specific types of medication taken during pregnancy in
a study of 911 women carried out by Forfar & Nelson in Scotland
in 1970.
- iron
- used to treat anaemia which causes a reduction in the blood's ability
to transport oxygen
- analgesics
- pain killers
- barbiturates
- early type of anti-anxiety drug - rarely used nowadays
- diuretics
- increase urine production
- anti-emetics
- reduce nausea
- antibiotics
- combat infections
- antihistamines
- treat allergies
- hormone
-e.g. diethyl stilbestrol (DES) given to reduce the risk of miscarriage
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Critical
periods in human development
There are critical
periods for the development of various systems in the embryo and fetus.
This knowledge can be used to track down the effect of teratogens and
alert doctors and women to the dangers of exposure to particular drugs
at various stages of pregnancy.
The
CNS (central nervous system) is at particular risk during the early
weeks of pregnancy - weeks 3-6.
Weeks
7 to 12 are thought to be the sensitive period for the development of
the external genitalia.
Legend
-
 = highly
sensitive period to teratogenic effects
-
 =
less sensitive period
Figure drawn from data in Krauer et al (1984)
Follow
this link to the Oregon
Museum of Science & Industry site which has pictures
showing the development various systems in the human embryo.
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Testing
drug safety in animals: International Guidelines
Experience
with thalidomide prompted a review
of drug safety testing guidelines. Before any medicine is licensed for
use in humans it
must be tested in animals. These tests examine the effects of the drug
on
- labour
and delivery
- newborn
vitality
- the
mother's ability to lactate
- the
growth of offspring whose mothers have received the drug during
pregnancy
- the
ability of offspring to successfully reproduce
In
these tests pregnant female animals are
treated during the last third of pregnancy and during lactation up to
weaning. Offspring
are monitored for growth and development after birth.
The
main and most important difference
between countries is the requirement in Japan and Canada for behavioural
observation of offspring. In the US, UK, and Scandanavian countries,
behavioural testing
is not mandatory. This table is taken from Riley & Vorhees.
Comparison
of International Guidelines
| |
U.S |
Canada
|
Scandanavia
|
U.K.
|
Japan
|
| Number
of species |
1 |
1 |
2 |
1 |
1 |
| Number
of doses |
2 |
3 |
3 |
3 |
3 |
| Number
of animals |
20 |
20 |
|
12 |
20 |
| Are
behavioural observations required? |
No |
Yes |
No |
No |
Yes |
In
addition it must be demonstrated that
animals that have been exposed to the drug 'in utero' are capable of
reproducing.
However
I have argued that
- tests
of reproductive function do not rule out the possibility that a drug
may have interfered with psychosexual differentiation
- psychosexual
differentiation is a developmental process that may be especially
sensitive to teratological insult
There
are a number of ways in which drug
exposure could effect psychosexual differentiation
- by
antagonising the effects of testosterone on target tissues within the
CNS
- by
interfering with neurotransmitters that are thought to mediate the
organisational effects of hormones on the brain
- by
inducing hepatic (liver) enzyme systems in the neonate and thereby
reducing androgen levels during the critical period of brain
development
For a
fuller discussion of this issue see
Kenyon & Malinek (1984).
Effects of
cimetidine on male rat sexual behaviour
There
is a strong body of information that
testosterone is involved in the psychosexual differentiation of the
mammalian brain.
Follow these links to related pages on psychosexual
differentiation and the
effects of hormones on sexual
behaviour .
An antiandrogen
might interfere with
psychosexual differentiation. Cimetidine (Tagamet) is used drug for the
treatment of
stomach ulcers - it is now available OTC (over-the-counter i.e. without
prescription ) it
is a weak antiandrogen. Anand & Van Thiel (1982) claimed that
cimetidine interferes
with psychosexual differentiation in animals.
| These graphs show the
effects of perinatal (pre- and neonatal) exposure to cimetidine on the
sexual behaviour of adult male rats (Anand & Van Thiel, 1982)
Male
rats exposed to cimetidine in utero, and whilst suckling showed:
- increased
mount latency
- reduced
mounting behaviour
when
they were exposed to a sexually receptive female rat for a 15 minute
test of their sexual behaviours
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Anand & Van
Thiel interpreted these results as indicating that cimetidine
significantly reduced
- sexual
motivation (mount latency) and
- sexual
performance (number of mounts)
Can
you see that this interpretation is flawed because the increase in
mount latency will inevitably lead to a reduction in the number of
mounts that can be made in a test session of fixed duration? There were
a number of other weaknesses in this study that make it difficult to
conclude that cimetidine poses a risk to human health.
Nevertheless
Anand & Van Thiel have highlighted the possibility that
ingestion of antiandrogens in pregnancy may threaten the process of
psychosexual differentiation.
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Testing
drug safety in animals: Behavioural tests
What is
surprising about Anand & van
Thiel's paper is that the research was carried out after
the drug was released for
use in humans. In other words, their work may highlight a weakness in
drug testing
procedures. Contemporary guidelines do not appear to acknowledge the
possibility that a
drug taken in pregnancy could interfere with the psychosexual
differentiation of the
unborn child. The realization of this danger prompted me to ask the
question:
What types of behaviour
are
examined by behavioural teratologists?
It
appears that simple tests that are
quick and cheap to administer are favoured.
The
table below presents the results of a
survey of japanese and american teratologists reported by Buelke-Sam
& Kimmel (1979).
- Simple
observational tests were preferred over more complex tests requiring
the use of specialised testing environments (e.g. operant chambers).
- Normally
male rats are used in this type of study.
Significant sex differences in performance on these tests has been
widely reported in the literature which suggests that any performance
effect(s) in drug exposed animals might be mediated by effects on
psychosexual differentiation.
Behavioural
tests used by teratologists in Japan & U.S.
|
Percentage of
labs using test in: |
|
| Type
of test |
Japan n=60
|
U.S.
n=69 |
Sex difference
on test? |
| General
behaviour |
68% |
33% |
|
| Motor
coordination |
82% |
51% |
|
| Reflex
|
86% |
49% |
|
| Activity
|
35% |
57% |
Yes |
| Emotionality
|
90% |
33% |
Yes |
| Maze
tests |
76% |
43% |
Yes |
| Avoidance
|
41% |
38% |
Yes |
| Operant
schedules |
2% |
25% |
Yes |
| Aggression
|
0% |
9% |
Yes |
| Sexual
behaviour |
0% |
9% |
Yes |
This
table shows how important it is to use
both male and female offspring - rather than just one sex- on
behavioural tests in order
to detect any behavioural change arising from an effect on psychosexual
differentiation.
The
argument for this position is
strengthened by studies showing that prenatal exposure alcohol,stress,
and drugs that
interfere with dopamine neurotransmission, affect psychosexual
differentiation.
Prenatal
stress feminises and demasculinises the behaviour of male rats
| Ward et al, (1972)
exposed female rats to stress whilst they were pregnant (prenatal
stress) or in the period after birth when they were suckling
their offspring (postnatal stress). The adult male
offspring of these stressed mothers were given six opportunities to
copulate with an estrous female. The diagrams show the percentage of
these perinatally stressed male rats that ejaculated or copulated on at
least one of six these tests. |
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 |
 |
Results:
- Many
of the prenatally stressed rats failed to copulate with female rats,
and very few of these males ejaculated.
- Prenataly
stressed male rats showed high levels of the typically female behaviour
'lordosis'.
- Postnatal
stress had no effect.
Conclusion:
These
results suggest that prenatal stress feminizes and demasculinizes
the behaviour of male rats. Stress may cause a decrease in the release
of testosterone in the developing male rat fetus.
|
This
explanation is supported by the observation that prenatal stress
reduces testosterone
in the male rat
fetus (Ward In Adler et al
(Eds.) Handbook of Behavioural Neurobiology, Volume 7. Reproduction)
Recent
research suggests that prenatal stress
does not have such dramatic effects on the gender role behavior of
girls and boys (Hines
et al 2002)
Prenatal
alcohol exposure alters adult expression of sexually dimorphic
behaviour in the rat
| McGiven et al (1984)
found that saccharin preference was altered in adult male and female
rats that had been exposed to alcohol during gestation.
The
sexual dimorphism normally observed in this behaviour was absent in
fetal alcohol-exposed rats.
The
lack of dimorphism appears to result from a masculinisation of the
exposed females and a feminisation of the exposed males.
Because
this is a fairly complex experiment, click
here to :
- use
the 'Separator Tool' to examine saccharine
preference in male and female control and alcohol-exposed groups
'one-group-at-a-time'
- use
the 'Overlayer Tool' to understand the
differential impact of alcohol-exposure on male and female rats.
|
 |
Perinatal
dopamine-related drugs demasculinise rats
| Hull et al (1984)
reported that the administration of haloperidol - a common neuroleptic
drug -to pregnant or lactating rats impaired the masculine sex
behaviour of their male offspring.
Prenatal
haloperidol did not affect testosterone concentration in fetuses.
Maternal
administration of apomorphine, a dopamine agonist, and of AMPT
(alpha-methyl-para-tyrosine), a DA synthesis inhibitor, also
demasculinised male behaviour but did not lower testosterone in
adulthood.
The
authors conclude that these drugs may act directly on neurons that
control masculine sexual behaviour, without lowering testosterone
prenatally or in adulthood.
|
 |
Point
to ponder
Can you think of any animal models that could be used to test the
safety of medicines taken in pregnancy? How would you experimentally
verify their efficacy? |
References & online
resources
- Anand
& Van Thiel, 'Prenatal and neonatal exposure to
cimetidine results in gonadal and sexual dysfunction in adult males',
Science , 218 , 493-494, 1982.
- Buelke-Sam
& Kimmel, 'Development and standardisation of
screening methods for behavioral teratology', Teratology ,
20 : 17-33, 1979.
- Hines
et al (2002). Prenatal Stress and Gender Role Behavior in
Girls and Boys: A Longitudinal, Population Study. Hormones
and Behavior Vol. 42, No. 2, September 2002.
From the abstract: We related
maternal self-reports of prenatal stress to childhood
gender role behavior in a prospective, population
study of 13,998 pregnancies
resulting in 14,138 offspring. Neither stress
reported during the first 18 weeks of pregnancy
nor stress reported from week 19 of pregnancy
to week 8 postnatal related to gender role behavior
in male offspring at the age of 42 months.
In female offspring, maternal reports
of stress during both periods showed
only small correlations with masculine-typical
behavior. ...Our results
suggest that prenatal stress does not influence
the development of gender role
behavior in boys and appears
to have relatively little, if any, influence on
gender role behavior in girls.
- Hull
et al, Science , 224 ,
1011-1013, 1984.
- Kenyon
& Malinek, Screening drugs for effects on
sexual differentiation, Neurobehavioral Toxicology and Teratology, 6,
1-2, 1984. (Available from Reprint Collection in Plymouth library)
- Krauer
et al, Drugs & Pregnancy , Academic Press,1984
- McGiven
et al, Science , 224 ,
896-898, 1984.
- Riley
& Vorhees, Handbook of Behavioral Teratology
(Available on Short Loan in Plymouth library)
- Slotkin,
'Fetal Nicotine or Cocaine Exposure: Which One is Worse?',Journal of
Pharmacology and Experimental Theraputics, June 1998 available online
at http://www.dukenews.duke.edu/nicotine/slotkin.htm
- Ward
et al, Science , 175 ,
82-85, 1972.
Supplementary reading
|
Doskoch (2001) Which is more toxic to a fetus -
antidepressants or maternal depression? Neuropsychiatry
Review 2/5 2001.
"Ten years ago, many
clinicians considered prescribing antidepressants to a pregnant woman
to be foolhardy. But recent data increasingly suggest otherwise. Most
studies indicate that antidepressants do not increase the risk of
obstetrical complications or birth defects (though more long-term
behavioral studies are needed). Conversely, evidence now suggests that
untreated maternal depression can have deleterious effects on
offspring, both by altering their neurobiology during fetal development
and by compromising care after birth."
The Chicago Project News - Fall 1996, The
Effects of Prenatal Exposure to Tobacco, Alcohol, and Cocaine,
by Daniel J. Kindlon, Ph.D. & Felton Earls, M.D.
"According to recent statistics, 17 percent of mothers
report having smoked cigarettes during pregnancy and 20 percent report
having used alcohol at some point during pregnancy (Ventura et al,
1994). When during development are the various effects of prenatal
exposure to tobacco, alcohol, or cocaine seen and what are these
effects? Does exposure relate to the development of academic
difficulties and behavior problems later? How might exposure interact
with family and neighborhood characteristics in producing such negative
outcomes? These are some of the questions being explored by the Project
on Human Development in Chicago Neighborhoods' Infant Study as they
assess the cognition, temperament, physical health, and caretaker's
characteristics of approximately 400-500 six-month old infants. In
preparation for this investigation, we prepared a literature review for
the National Institute of Justice on prenatal exposure to tobacco,
alcohol, and cocaine, including information gathered from recent
comprehensive reviews of research on both humans and animals. Our aim
is to expand on this base of knowledge as we complete data collection
for the study we have undertaken."
|
Cocaine Use During
Pregnancy: Its Effects On Infant Development and Implications for
Adoptive Parents
by Judith Schaffer, M.A.
"Prospective adoptive parents, as well as parents who
have recently adopted infants, need to be aware that when a pregnant
woman uses cocaine during her pregnancy, it crosses the placenta and
causes considerable damage to the developing fetus. Although cocaine is
thought to damage many organ systems, the developing central nervous
system of the fetus is especially sensitive to this powerful stimulant.
Such damage has been implicated in a variety of developmental problems
for the infant and later for the child.
A lack of knowledge about the symptoms associated with damage to the
central nervous system can lead parents and others to mistakenly
attribute them to psychological problems associated with foster care
and adoption. It is therefore important that families who adopt
infants, as well as agency workers and others who place them, be
familiar with the growing research about the unique characteristics of
these infants. It is also important to be familiar with the kinds of
evaluations available which may help you to determine whether or not an
infant has been cocaine-exposed, the special needs of these infants,
and the intensive parenting that they appear to require." |
| Behavioral
Studies of Drug-Exposed Offspring: Methodological Issues in Human and
Animal Research
National
Institute on Drug Abuse Monograph 164:
- Prenatal
drug Exposure: Behavioral Functioning in Late Childhood and Adolescence.
S.L. Hans, NIDA Monograph 164, pp. 261-276. Reviews the current state
of knowledge on the long term effects of abused drugs on childrens'
development.
- Prenatal
Exposure to Drugs of Abuse: Methodological Considerations and Effects
on Sexual Differentiation
RF McGivern & RJ Handa, NIDA Monograph 164, pp. 78-124
- The
Effects of Prenatal Cocaine Exposure on Subsequent Learning in the Rat,
EP Riley & MH LaFiette, NIDA Monograph 164, pp. 53-77
- Long-Term
Effects of Developmental Exposure to Cocaine on Learned and Unlearned
Behaviours,
CV Vorhees, NIDA Monograph 164, pp. 3-52
- Drug
Effects: A Search for Outcomes ,
B. Zuckerman, NIDA Monograph 164, pp. 277-287
- Assessment
of the Effects of Developmental Toxicants: Pharmacological and Stress
Vulnerability of Offspring,
LP Spear, NIDA Monograph 164, pp. 125-145
|
COCAINE AND
PREGNANCY ,
by Phillip Coffin of The Lindesmith Center.
"The rise in cocaine use and appearance of crack cocaine
in the 1980s spurred fears about its effects on the developing fetus.
Cocaine use during pregnancy is certainly inadvisable, yet many of the
initial reports cited dangers that later studies do not support, and
policies fostered during those years may have caused more harm than
good. Recent press and politics have not reflected changes seen in the
scientific realm. " |
Organization of
Teratology Information Services
publishes a number of useful Fact Sheets, including one on Prozac with
answers to questions that many mothers will ask, for example
Will taking Prozac have any effect on my baby's behavior
and development?
"Studies have begun to look at the possible long-term effects on
infants exposed to Prozac during pregnancy. Prozac affects the mother
by changing chemical levels in the brain. These changes could also have
an effect on fetal brain development. One study examined development in
children averaging three years of age and did not find differences
between exposed and unexposed children. The first completed study of
behavior and development was reassuring, however, more studies are
needed before we can be certain of the effects on the fetal brain." |
Fetal
Alcohol Syndrome
"In 1973, Jones and Smith coined the term "fetal alcohol
syndrome" (FAS) to describe a pattern of abnormalities observed in
children born to alcoholic mothers. It was originally postulated that
malnutrition might be responsible for these defects. However, the
pattern of malformation associated with FAS is not seen in children
born to malnourished women, and alcohol has been found to be acutely
toxic to the fetus independently of the effects of malnutrition ." |
Evolution
of Our Understanding of Methylmercury as a Health Threat ,
Chiho Watanabe and Hiroshi Satoh, Department of Environmental Health
Sciences, Tohoku University School of Medicine, Sendai, Japan
"Methylmercury (MeHg) is recognized as one of the most
hazardous environmental pollutants, primarily due to endemic disasters
that have occurred repeatedly. A review of the earlier literature on
the Minamata outbreak shows how large-scale poisoning occurred and why
it could not be prevented. With the repeated occurrences of MeHg
poisoning, it gradually became clear that the fetus is much more
susceptible to the toxicity of this compound than the adult. Thus,
recent epidemiologic studies in several fish-eating populations have
focused on the effects of in utero exposure to MeHg. Also, there have
been many studies on neurobehavioral effects of in utero exposure to
methylmercury in rodents and nonhuman primates. The results of these
studies revealed that the effects encompass a wide range of behavioral
categories without clear identification of the functional categories
distinctively susceptible to MeHg. The overall neurotoxicity of MeHg in
humans, nonhuman primates, and rodents appears to have similarities.
However, several gaps exist between the human and animal studies. By
using the large body of neurotoxicologic data obtained in human
populations and filling in such gaps, we can use MeHg as a model agent
for developing a specific battery of tests of animal behavior to
predict human risks resulting from in utero exposure to other chemicals
with unknown neurotoxicity. Approaches developing such a battery are
also discussed. -- Environ Health Perspect 104(Suppl 2):367-379 (1996)
" |
Appropriate
End Points for the Characterization of Behavioral Changes in
Developmental Toxicology,
Vincenzo Cuomo (1), Maria A. De Salvia (1), Simona Petruzzi (2), and
Enrico Alleva (2) (1)Institute of Pharmacology, University of Bari,
Bari, Italy; (2)Behavioral Pathophysiology Section, Istituto Superiore
di Sanità, Rome, Italy
"The present paper is devoted to second- and higher-tier
test methods for the characterization of behavioral changes produced in
rodents by exposure to noxious agents during development. The paper
analyzes a series of end points that are informative about specific
processes and underlying regulatory mechanisms but require greater
technical sophisti cation and larger investments than first-tier end
points. This applies to ultrasonic emissions in successive postnatal
periods; to mother-pup interactions, including appropriate
cross-fostering controls; to social (including sexual) interaction
tests from the infantile to the young adult stage; and to a variety of
conditioning and learning tests u sing both positive and negative
reinforcement. -- Environ Health Perspect 104(Suppl 2):307-315 (1996) "
|
Neurobehavioral
Aspects of Developmental Toxicity Testing,
Beate Ulbrich(1) and Anthony K. Palmer(2), (1) Bundesinstitut
für Arzneimittel und Medizinprodukte, Berlin, Germany; (2)
Huntingdon Research Centre, Huntingdon, Cambridgeshire, Great Britain
"Tests for detection of neurobehavioral changes in the
offspring have been a regulatory requirement in developmental toxicity
testing of drugs for almost 20 years. Keeping their purpose of hazard
identification and risk assessment for humans in mind, investigators
and agency reviewers have become deeply ingrained with some stereotyped
behaviors with respect to such relevant issues as choice of animal
species and data evaluation. Other problematic areas of study design
and conduct, selection of litter representatives for testing, what
methods to combine in a testing battery, and statistical treatment of
results and their interpretation, will need more research and
discussion in the future. -- Environ Health Perspect 104(Suppl
2):407-412 (1996)" |
Animal
Models in Alcohol Research
"Animals are used in alcoholism research for the same
reasons that they are used in all medical research: to understand the
causes of disease and to develop new treatments. Animals are used in
three principal ways in research on alcoholism: to model the drinking
behavior of human alcoholics, to learn from the brain and other organs
of drinking animals how brain chemistry leads to a drinking behavior,
and to study how alcohol damages organs. No animal model completely
reproduces all the features of the human disease. On the other hand,
individual features of alcoholism can be studied in animals in great
detail. Moreover, the researcher has full control over experimental
conditions such as nutrition, environment, species, and ancestry. This
Alcohol Alert reviews animal research designed to answer questions
pertaining to human alcohol use and abuse. " |
The
health and psychological consequences of cannabis use
"The following are the major possible adverse effects of chronic, heavy
cannabis use which remain to be confirmed by further research:
- an
increased risk of developing cancers of the aerodigestive tract, i.e.
oral cavity, pharynx, and oesophagus;
- an increased risk of
leukemia among offspring exposed while in utero;
- a decline in
occupational performance marked by underachievement in adults in
occupations requiring high level cognitive skills, and impaired
educational attainment in adolescents;
- birth defects
occurring among children of women who used cannabis during their
pregnancies."
|
| Profet, M. 1992.
Pregnancy sickness as adaptation: A deterrent to maternal ingestion of
teratogens. In Barkow, J. H., Cosmides, L., and Tooby, J. (eds.) The
Adapted Mind: Evolutioanry Psychology and the Generation of Culture.
Oxford University Press, NY.
Profet argues that
"pregnancy sickness" (a.k.a., "morning sickness") is not a sickness at
all, but an adaptive response to avoid potential teratogens. Its
sympoms all cause the avoidance of aromatic foods. The aromatic nature
of these foods was originally a signal that such foods contain
compounds which can be dangerous.
Here is an abstract
of Profet's argument
|
Copyright Dr.
C.A.P. Kenyon 1994-2006