lithium-chloride and 1-(3-chlorophenyl)biguanide

A taste associated with emetic drugs produces conditioned disgust reactions in rats (predominantly gaping), unlike nonemetic drugs that can still produce conditioned taste avoidance but not conditioned disgust. That difference suggests nausea is a prerequisite for learning disgust reactions to tastes. Depletion of forebrain serotonin (5-HT) by 5,7-dihydroxytryptamine (5,7-DHT) lesions of the dorsal raphe nucleus and median raphe nucleus prevents LiCl-induced conditioned disgust reactions (Limebeer et al., 2004). Here we demonstrate that partial depletion of 5-HT in the insular cortex (IC) prevents LiCl-induced conditioned disgust reactions. Furthermore, a double dissociation occurred in the partial regulation of disgust and taste avoidance by selective 5-HT(3) receptor antagonism/agonism in the posterior (granular) region of the IC and the anterior (dorsal agranular) region of the IC, respectively. Intracranial administration of the 5-HT(3) receptor antagonist, ondansetron (OND), to the posterior IC impaired the establishment of LiCl-induced conditioned gaping reactions, but not LiCl-induced conditioned taste avoidance (CTA). Likewise, posterior IC administration of the 5-HT(3) receptor agonist m-chlorophenylbiguanide (mCPBG) enhanced the establishment of LiCl-induced conditioned gaping and produced conditioned gaping on its own (which was prevented by intracranially administered OND), with no effect on CTA. On the other hand, anterior IC administration of OND partially reduced the establishment of LiCl-induced CTA, and mCPBG produced a weak CTA, both without effect on gaping. These results suggest that activation of 5-HT(3) receptors in the posterior IC is important for the production of nausea-induced conditioned disgust reactions, while activation of 5-HT(3) receptors in the anterior IC are involved in the production of CTA.

Topics: 5,6-Dihydroxytryptamine; Animals; Avoidance Learning; Biguanides; Cerebral Cortex; Conditioning, Classical; Emotions; Lithium Chloride; Male; Nausea; Ondansetron; Rats; Rats, Sprague-Dawley; Receptors, Serotonin, 5-HT3; Saccharin; Serotonin 5-HT3 Receptor Agonists; Serotonin 5-HT3 Receptor Antagonists; Taste

In the present study, we investigated the participation of central 5-HT(2B/2C) and 5-HT(3) receptors in the salt intake induced by sodium depletion in Wistar male rats. Sodium depletion was produced by the administration of furosemide associated with a low salt diet. Third ventricle injections of mCPP, a 5-HT(2B/2C) agonist, at doses of 80, 160 and 240 nmol, promoted a dose-dependent reduction in salt intake in sodium-depleted rats. The inhibitory effect produced by central administration of mCPP was abolished by the central pretreatment with SDZ SER 082, a 5-HT(2B/2C) antagonist. Similar results were obtained with third ventricle injections of m-CPBG (80, 160 and 240 nmol), a selective 5-HT(3) agonist that also induced a dose-related decrease in salt intake in sodium-depleted rats. The central pretreatment with LY-278,584, a selective 5-HT(3) receptor antagonist, was able to impair the salt intake inhibition elicited by third ventricle injections of m-CPBG. Central administration of each one of the antagonists alone or a combination of both antagonists together did not significantly change salt intake after sodium depletion. On the other hand, the central administration of both mCPP and m-CPBG, in the highest dose used to test their effect on salt intake (240 nmol), was unable to modify blood pressure in sodium-depleted rats. It is concluded that: (1) pharmacological activation of central 5-HT(2B/2C) and 5-HT(3) receptors diminishes salt intake during sodium depletion, (2) an inhibitory endogenous drive exerted by central 5-HT(2B/2C) and 5-HT(3) receptors does not seem to exist and (3) the reduction in salt intake generated by the pharmacological activation of these central receptors is not produced by an acute hypertensive response.

Topics: Animals; Biguanides; Blood Pressure; Diuretics; Dose-Response Relationship, Drug; Drinking; Drug Interactions; Feeding Behavior; Furosemide; Indazoles; Indoles; Injections, Intraventricular; Lithium Chloride; Male; Piperazines; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2B; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Saccharin; Serotonin Antagonists; Serotonin Receptor Agonists; Sodium; Time Factors; Tropanes