Clinical observations show that there is considerable individual variability in the response to the addictive properties of drugs. This individual variability needs to be taken into account in animal models of addiction. Like humans, only some rats readily self-administer low doses of psychostimulants. The individual animals at risk can be identified on the basis of their response to environmental or pharmacological challenges. This predisposition to develop self-administration can be induced by repeated treatment with amphetamine. These results may help elucidate the neurobiological basis of addiction liability observed in both rats and humans.
It is well known that the hypothalamo-pituitary-adrenal (HPA) axis is altered by early environmental experiences, particularly in the perinatal period. This may be one mechanism by which the environment changes the physiology of the animal such that individual differences in adult adaptative capabilities, such as behavioral reactivity and memory performance, are observable. To determine the origin of these behavioral individual differences, we have investigated whether the long-term influence of prenatal and postnatal experiences on emotional and cognitive behaviors in adult rats are correlated with changes in HPA activity. To this end, prenatal stress of rat dams during the last week of gestation and postnatal daily handling of rat pups during the first 3 weeks of life were used as two environmental manipulations. The behavioral reactivity of the adult offspring in response to novelty was evaluated using four different parameters: the number of visits to different arms in a Y-maze, the distance covered in an open field, the time spent in the corners of the open field, and the time spent in the open arms of an elevated plus-maze. Cognitive performance was assessed using a water maze and a two-trial memory test. Adult prenatally stressed rats showed high anxiety-like behavior, expressed as an escape behavior to novelty correlated with high secretion of corticosterone in response to stress, whereas adult handled rats exhibited low anxiety-like behavior, expressed as high exploratory behavior correlated with low secretion of corticosterone in response to stress. On the other hand, neither prenatal stress nor handling changed spatial learning or memory performance. Taken together, these results suggest that individual differences in adult emotional status may be governed by early environmental factors; however, perinatal experiences are not effective in influencing adult memory capacity.
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