PRENATAL STRESS IN RATS FACILITATES AMPHETAMINE-INDUCED SENSITIZATIONAND INDUCES LONG-LASTING CHANGES IN DOPAMINE-RECEPTORS IN THE NUCLEUS-ACCUMBENS

Exposure of rats to restraint stress during late pregnancy produces of fspring with a variety of behavioral and neurobiological alterations. It has been suggested that prenatal stress leads to long-lasting chang es in the hypothalamo-pituitary-adrenal axis in the offspring. One fea ture of prenatally-stressed rats is a susceptibility to amphetamine se lf-administration. Since this behavior has been related to amphetamine -induced sensitization and the activity of the mesolimbic dopamine sys tem, we measured dopamine receptor densities and amphetamine-induced s ensitization in these animals. The motor response to the first adminis tration of amphetamine was similar in both prestressed and unstressed groups of adult animals, but after repeated drug injections, behaviora l sensitization was observed sooner in the prenatally-stressed rats th an in the controls. In separate groups of adult animals, densities of D1, D2 and D3 dopamine receptor subtypes in the striatum and nucleus a ccumbens were measured in prenatally-stressed and control rats by quan titative autoradiography using [H-3]SCH23390, [H-3]sulpiride and [H-3] 7-OH-DPAT as ligands respectively. Prenatal stress was found to produc e 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 nuc leus accumbens; (iii) a significant decrease in D3 receptor binding in both the shell (-16%) and the core (-26%) of the nucleus accumbens. T hese observations indicate that prenatal stress induces long-lasting c hanges in the dopamine sensitivity of the nucleus accumbens and in the capacity to develop amphetamine-induced sensitization in adulthood. T he possible relationship between an impaired control of corticosterone secretion in prenatally-stressed animals and long-term changes in the mesolimbic dopamine system is discussed.