Individual vulnerability to substance abuse and affective disorders: role of early environmental influences.
neurotox res. 2002-01-01; 4(4): 281-296
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1. Neurotox Res. 2002 Jun;4(4):281-96.
Individual vulnerability to substance abuse and affective disorders: role of
early environmental influences.
Koehl M(1), Lemaire V, Mayo W, Abrous DN, Maccari S, Piazza PV, Le Moal M, Vallée
(1)Laboratoire de Psychobiologie des Comportements Adaptatifs – INSERM U.259,
Université Victor Ségalen Bordeaux 2, Institut François Magendie, Rue Camille
Saint-Saëns, 33077 Bordeaux Cedex, France.
One of the most important questions raised by modern psychiatry and experimental
psychopathology is the origin of mental diseases. More concisely, clinical and
experimental neurosciences are increasingly concerned with the factors that
render one individual more vulnerable than another to a given pathological
outcome. Animal models are now available to understand the sources of individual
differences for specific phenotypes prone to behavioral disadaptations. Over the
last 10 years we have explored the consequences of environmental perinatal
manipulations in the rat. We have shown that prenatal stress is at the origin of
a wide range of physiological and behavioral aberrances such as alterations in
the activity of the hormonal stress axis, increased vulnerability to drug of
abuse, emotional liability, cognitive impairments and predisposition to
pathological aging. Taken together, these abnormalities define a bio-behavioral
syndrome. Furthermore, the cognitive disabilities observed in prenatally-stressed
rats were recently related to an alteration of neurogenesis in the dentate gyrus,
thus confirming the impact of early life events on brain morphology. A second
model (handling model) has also been developed in which pups are briefly
separated from their mothers during early postnatal life. In contrast with
prenatally-stressed animals, handled rats exhibited a reduced emotion response
when confronted with novel situations and were protected against age-induced
impairments of both the hormonal stress axis and cognitive functions. Taken
together, the results of these investigations show that the bio-behavioral
phenotype that characterizes each individual is strongly linked to the nature and
timing of perinatal experience. Furthermore, data collected in
prenatally-stressed animals indicate that this model could be used profitably to
understand the etiology and pathophysiology of affective disorders.