DOPAMINE ENHANCES SOMATOSTATIN RECEPTOR-MEDIATED INHIBITION OF ADENYLATE-CYCLASE IN RAT STRIATUM AND HIPPOCAMPUS

Although there is evidence that suggests that dopamine (DA) has stimul atory effects on somatostatinergic transmission, it is unknown to date if DA increases the activity of the somatostatin (SS) receptor-effect or system in the rat brain, In this study, we evaluated the effects of the administration of DA and the DA D-1-like (D-1, D-5) receptor anta gonist SCH 23390 and the D-2-like (D-2, D-3, D-4) receptor antagonist spiperone on the SS receptor-adenylate cyclase (AC) system in the Spra gue-Dawley rat striatum and hippocampus. An intracerebroventricular in jection of DA (0.5 mu g/rat) increased the number of SS receptors and decreased their apparent affinity in the striatum and hippocampus 15 h r after its administration, The simultaneous administration of the DA receptor antagonists SCH 23390 (0.25 mg/kg, ip) and spiperone (0.1 mg/ kg, ip) before DA injection partially prevented the DA-induced increas e in SS binding, The administration of SCH 23390 plus spiperone alone produced a significant decrease in the number of SS receptors in both brain areas studied at 15 hr after injection, an effect that disappear ed at 24 hr, The increased number of SS receptors in the DA-treated ra ts was associated with an increased capacity of SS to inhibit basal an d forskolin (FK)-stimulated (AC) activity in the striatum and hippocam pus at 15 hr after injection, This effect had disappeared at 24 hr, By contrast, basal and FK-stimulated enzyme activities were unaltered af ter DA injection, No significant changes in the levels of the alpha(1) (alpha(i1) + alpha(i2)) subunits were found in DA-treated rats as com pared with control rats, In addition, the immunodetection of the alpha (i1) or alpha(i2) subunits showed no significant changes in their leve ls in DA-treated rats when compared,vith controls, DA injection also i nduced an increase in SS-like immunoreactive content in the rat striat um but not hippocampus at 15 hr after administration and returned to c ontrol values at 24 hr, These results provide direct evidence of a fun ctional linkage between the dopaminergic and somatostatinergic systems at the molecular level. (C) 1997 Wiley-Liss, Inc.