Prenatal stress in rats facilitates amphetamine-induced sensitization and induces long-lasting changes in dopamine receptors in the nucleus accumbens.

ABSTRACT

Exposure of rats to restraint stress during late pregnancy produces offspring with a variety of behavioral and neurobiological alterations. It has been suggested that prenatal stress leads to long-lasting changes in the hypothalamo-pituitary-adrenal axis in the offspring. One feature of prenatally-stressed rats is a susceptibility to amphetamine self-administration. Since this behavior has been related to amphetamine-induced sensitization and the activity of the mesolimbic dopamine system, we measured dopamine receptor densities and amphetamine-induced sensitization in these animals. The motor response to the first administration of amphetamine was similar in both prestressed and unstressed groups of adult animals, but after repeated drug injections, behavioral sensitization was observed sooner in the prenatally-stressed rats than in the controls. In separate groups of adult animals, densities of D1, D2 and D3 dopamine receptor subtypes in the striatum and nucleus accumbens were measured in prenatally-stressed and control rats by quantitative autoradiography using [3H]SCH23390, [3H]sulpiride and [3H]7-OH-DPAT as ligands respectively. Prenatal stress was found to produce the following alterations in the adult offspring (i) no significant change in D1 receptor binding in either striatum or nucleus accumbens; (ii) a significant (+24%) increase in D2 receptor binding in the nucleus accumbens; (iii) a significant decrease in D3 receptor binding in both the shell (-16%) and the core (-26%) of the nucleus accumbens. These observations indicate that prenatal stress induces long-lasting changes in the dopamine sensitivity of the nucleus accumbens and in the capacity to develop amphetamine-induced sensitization in adulthood. The possible relationship between an impaired control of corticosterone secretion in prenatally-stressed animals and long-term changes in the mesolimbic dopamine system is discussed.