EFFECT OF SULPIRIDE ON SOMATOSTATIN RECEPTORS, SOMATOSTATIN-LIKE IMMUNOREACTIVITY AND MODULATION OF ADENYLYL-CYCLASE ACTIVITY IN THE RAT-BRAIN

The present study investigates the effects of the administration of an intracerebroventricular (i.c.v.) dose of 500 mu g/rat of the neuroleptic (-) sulpiride on somatostatin-like immunoreactivity (SSLI) levels, I-125-Tyr(11)-SS binding to its specific receptors, SS-modulated adenylyl cyclase (AC) activity and the pertussis toxin (PTX) substrates measured by toxin-catalysed ADP ribosylation of the alpha-subunits from G-proteins. (-) Sulpiride significantly decreased the SSLI levels in the frontoparietal cortex at 30 min but was without effect on the SSLI concentration in the striatum. This decrease had disappeared within 24hr. The administration of (-) sulpiride produced a significant increase in the number of I-125-Tyr(11)-SS receptors and a significant reduction in their affinity at 30 min after injection in the striatum without affecting the frontoparietal cortex. The effects of the (-) sulpiride injection had disappeared after 24 hr. This change in SS binding was not due to a direct effect of (-) sulpiride on these receptors since no effect on binding was produced by high concentrations of (-) sulpiride (10(-5) M) when added in vitro. No significant differences were seen in either brain region for the basal or the forskolin (FK)-stimulated AC enzyme activities in the control and (-) sulpiride groups. In the (-) sulpiride group, the capacity of SS to inhibit FK-stimulated AC in the frontoparietal cortex was significantly higher than in the control group with no significant difference in the striatum. These results correlate with the increase of a 41 kDa PTX substrate, presumably the alpha-i-subunit of Gi substrates in frontoparietal cortex and striatum 30 min after (-) sulpiride administration with respect to the corresponding controls.