STRESS PROMOTES MAJOR CHANGES IN DOPAMINE RECEPTOR DENSITIES WITHIN THE MESOACCUMBENS AND NIGROSTRIATAL SYSTEMS S. CABIB,* L. GIARDINO,² L. CALZA u ,‡ M. ZANNI,§ A. MELE¶ and S. PUGLISI-ALLEGRA** *Institute Psicobiologia e Psicofarmacologia viale K. Marx 43, Rome 00137, Italy ²Institute Clinico O.R.L. II a , University of Milano, Milano, Italy ‡Institute Fisiologia Umana, University of Cagliari, Cagliari, Italy §Department Patologia Neurosensoriale, University of Modena, Modena, Italy ¶Department Genetica e Biologia Molecolare, University ‘‘La Sapienza’’, Rome, Italy **Department Psicologia (Neuroscience Section), University ‘‘La Sapienza’’, Rome, Italy Abstract––This study investigated the effects of stress on brain dopamine receptor densities in two inbred strains of mice. Analysis of [ 3 H]SCH23390 binding by quantitative autoradiography revealed that repeated restraint stress significantly increases D 1 -like receptor density in the nucleus accumbens of mice of the DBA/2 strain whist reducing it in the caudate–putamen of C57BL/6 mice. No significant changes in D 2 -like receptor quantified by [ 3 H ]()-sulpiride binding were observed in caudate, substantia nigra and accumbens of stressed C57BL/6 mice. Instead, in DBA/2 mice, stress significantly increased D 2 -like receptor density in the nucleus accumbens whilst reducing it in the substantia nigra. Finally, stress significantly increased D 2 -like receptor density within the ventral tegmental area of C57BL/6 mice whilst significantly reducing it in mice of the DBA/2 strain. These results indicate that stress promotes major changes in mesoaccumbens and nigrostriatal dopamine receptor densities. The direction of these changes depends on receptor subtype, brain area and strain. Moreover, the opposite changes of D 2 -like receptor densities promoted by stress in the ventral tegmental area of the two inbred strains of mice suggest that mesoaccumbens dopamine autoreceptors density might be controlled by a major genotypestress interaction.  1998 IBRO. Published by Elsevier Science Ltd. Key words: autoradiography, autoreceptors, D 1 -like receptors, D 2 -like receptors, genotype, ventral tegmental area. Neural adaptation promoted by environmental pres- sure (stressful experiences) in mature organisms represents a relevant field of study for preclinical research since converging evidences point to the contribution of stress in the induction or exacerba- tion of different behavioural disorders. 2,3,13,19,27,38,45 Considerable evidence also implies disturbances of brain dopamine (DA) function in the pathophysio- logy of these disorders. 19,36–38,46,49,53,54,56,58 More- over, changes in DA metabolism and release have been observed in response to stressful stimuli, 1,6,11,16,22,24,41,44,47 and a number of data in- dicate that chronic or repeated stressful experiences promote alterations of brain DA function- ing. 7,10,12,21,35,43,48,51,52 Thus, a major involvement of brain DA systems in the stress-induced neural adaptation may be envisaged. The stress-induced adaptation of brain DA func- tioning may involve DA receptors since DA receptor densities are a ffected by altered extracellular DA levels. 28 Such a possibility would be of great clinical relevance since altered DA receptor densities have been reported by post mortem studies in psychiatric patients. 27,36,37,49,53 Nevertheless, surprisingly few studies have investigated the possibility of stress- induced changes in brain DA receptors in animal models. 35,40,43 Moreover, contrasting results were reported by these studies, which do not allow any firm conclusion to be reached about the effects of stress on brain DA receptors. Comparative studies in inbred strains of mice may represent a useful strategy to dissect alternative effects of experimental manipulations on brain func- tioning in relation to behavioural expression. 42 Moreover, these studies represent a preliminary stage in behavioural genetic research since they allow quantitative scales to be established and suggest correlations to be tested in recombinant inbred strains. 7,34,39 It has been previously shown that To whom correspondence should be addressed. A bbreviations: CP, caudate–putamen; DA, dopamine; NAS, nucleus accumbens septi; SN, substantia nigra; VTA, ventral tegmental area. Pergamon N euroscience Vol. 84, No. 1, pp. 193–200, 1998 Copyright  1998 IBRO. Published by Elsevier Science Ltd Printed in Great Britain. All rights reserved 0306–4522/98 $19.00+ 0.00 PII: S0306-4522(97)00468-5 193