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 micrograms/rat of the neuroleptic (-) sulpiride on somatostatin-like immunoreactivity (SSLI) levels, 125I-Tyr11-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 24 hr. The administration of (-) sulpiride produced a significant increase in the number of 125I-Tyr11-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.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain somatostatinergic system at late pregnancy, parturition and the early postpartum period in the rat.

During pregnancy and postpartum rats experience a wide variety of behavioural changes. Since the somatostatinergic system has been implicated in the control of some of these changes, the present study examined somatostatin (SS) content and specific binding in the frontoparietal cortex and hippocampus of non-pregnant, pregnant (17 to 18 days), parturition and postpartum (10 and 30 days) rats as well as in ovariectomized rats which were or were not treated with estradiol valerianate. The content of somatostatin-like immunoreactivity (SSLI) was increased at 17 days of pregnancy in frontoparietal cortex and decreased at parturition and 10 days postpartum in that region and the hippocampus under study when compared with SSLI levels in non-pregnant rats. At 30 days postpartum the SSLI content returned to non-pregnant values in both brain regions. Scatchard analysis showed that the decrease in [125I]Tyr11-SS binding observed at 17 days of pregnancy in the frontoparietal cortex was due to the decrease in the number of SS receptors. In contrast, on the day of delivery the number of SS receptors in the same brain region increased. The affinity of the SS receptors was consistently unchanged in pregnant and non-pregnant rats in both regions. At 10 days postpartum the value of specific binding of the tracer to SS receptors in the frontoparietal cortex was not significantly different from that in the non-pregnant rats, although the actual number of receptors was slightly higher. Pregnancy did not change SS binding in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of maternal exposure to nicotine in the rat on level and binding of somatostatin in brain of developing offspring.

The effect of maternal exposure to nicotine on the level of somatostatin and specific binding in frontoparietal cortex and hippocampus of developing offspring was investigated. Sprague-Dawley rats were injected subcutaneously, throughout the pregnancy and the nursing period, with either: 3 mg/kg nicotine base or saline vehicle. In the offspring of control rats, the level of somatostatin-like immunoreactivity peaked at day 10 in the frontoparietal cortex, whereas the level of immunoreactivity in the hippocampus was the highest on day 30. Maternal exposure to nicotine caused enhanced levels of immunoreactivity in the frontoparietal cortex, on the day of birth and in the hippocampus, up to day 10. The maximum specific binding of somatostatin to the receptors in membranes from the frontoparietal cortex, peaked at 10 days of age in the offspring of control rats. The number of somatostatin receptors in cortical (but not in hippocampal) membranes was significantly decreased in the 0- to 10-day-old offspring of the nicotine-treated rats. Despite transient alterations in the number of somatostatin receptors, the affinity of the sites for somatostatin was consistently unchanged. The levels of somatostatin-like immunoreactivity and the number of somatostatin receptors in the frontoparietal cortex and hippocampus was comparable in the 30-day-old offspring of the control and nicotine-treated rats.

The effect of chronic administration of nicotine and withdrawal on somatostatin concentration and binding in brain of rat.

The effects of chronic administration of nicotine (20 or 30 days) and its withdrawal on somatostatin-like immunorectivity and the binding of 125I-Tyr11-somatostatin in the frontoparietal cortex and hippocampus of the rat were investigated. Chronic administration of nicotine resulted in a decrease in the total number of specific somatostatin receptors, while the affinity of the receptors was unaltered and somatostatin-like immunoreactivity was unchanged in both areas of the brain. Three weeks after ending chronic exposure to nicotine in the second experimental group, the number of somatostatin receptors had returned to the same values as those of saline-treated rats.

Effects of acute nicotine and mecamylamine administration on somatostatin concentration and binding in the rat brain.

Since nicotine and somatostatin have regulatory effects on locomotor activity it was of interest to determine whether the receptors for somatostatin are modulated by the cholinergic nicotine-like effects. An i.v. dose of 0.3 mg/kg nicotine induced an increase in the concentrations of somatostatin-like immunoreactivity at 4 min in the parietal cortex and at 15 min in the hippocampus. These changes were associated with a significant increase in the total number of specific somatostatin receptors in the parietal cortex at 15 min and in the hippocampus at 30 min following injection. To determine if the above mentioned changes are related to the nicotine activation of central nicotine-like acetylcholine receptors, a cholinergic nicotinic blocking agent, mecamylamine, was administered before the nicotine injection. Pretreatment with mecamylamine (5.0 mg/kg i.v.) prevented the nicotine-induced changes in somatostatin level and binding in both brain areas. Mecamylamine alone had no observable effect on the somatostatinergic system. These results suggest that the somatostatinergic system can be regulated by nicotine-like acetylcholine receptors and may be involved in some of the behavioral central effects of nicotine.