Role of 5-HT(1A) and 5-HT(7) receptors in the facilitatory response induced by 8-OH-DPAT on learning consolidation.

The present study further explored the mechanisms involved in the facilitatory effect induced by (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on learning consolidation. For this purpose, we analyzed in parallel the effects of LY215840 and ritanserin, two 5-HT(2) receptor antagonists with high affinity for the 5-HT(7) receptor, and WAY100635, a selective 5-HT(1A) receptor antagonist, on the facilitatory effect induced by 8-OH-DPAT on learning consolidation. We also determined whether LY215840 and/or ritanserin could be beneficial in restoring a deficient learning condition. Using the model of autoshaping task, post-training injection of LY215840 or WAY100635 had no effect on learning consolidation. However, both drugs abolished the enhancing effect of 8-OH-DPAT, with LY215840 being slightly more effective than WAY100635 in this respect. Ritanserin produced an increase in performance by itself and also abolished the effect of 8-OH-DPAT. Remarkably, selective blockade of 5-HT(2A) and 5-HT(2B/2C) receptors with MDL100907 and SB200646, respectively, failed to alter the 8-OH-DPAT effect. LY215840 and ritanserin, at the doses that inhibited the 8-OH-DPAT-induced response, reversed the learning deficits induced by scopolamine and dizocilpine. The present results suggest that the enhancing effect produced by 8-OH-DPAT on learning consolidation involves activation of 5-HT(1A) receptors and an additional mechanism, probably related to the 5-HT(7) receptor. Blockade of 5-HT(2) receptors, and perhaps of 5-HT(7) receptors as well, may provide some benefit in reversing learning deficits associated with decreased cholinergic and/or glutamatergic neurotransmission.

Inhibition of the response to pain by the action of serotonin and carbachol topically applied to the area postrema of conscious guinea pigs.

The amplitude of vocalization and the motor defense response evoked by painful electrical stimulation were recorded in unanesthetized guinea pigs submitted to topical application of 1.0 microgram/microliter carbachol to the area postrema. Carbachol was found to have an analgesic effect. A similar application of 3.0 micrograms/microliter 5-hydroxytryptamine (5-HT) also had an analgesic effect, whose duration, however, was only half that of carbachol and whose intensity was lower, although the latency of the response was 2 seconds for both drugs. When 100 micrograms/microliter lysergic acid was applied to the area postrema the results did not differ significantly from control values, with only a small tendency toward hyperalgesia being observed. The present results, taken together with those obtained with noradrenalin in a previous study, suggest that the rich endowment of neurotransmitters in the area postrema may indicate a polyvalent analgesic mechanism able to provide a finer regulation of analgesia.