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

Using a combination of the paradigm of conditioned taste aversion (CTA) and of the paradigm of social interactions, we report here that in the rat, eating while anxious may result in long-term alterations in social behavior. In the conventional CTA, the subject learns to associate a tastant (the conditioned stimulus, CS) with delayed toxicosis (an unconditioned stimulus, UCS) to yield taste aversion (the conditioned response, CR). However, the association of taste with delayed negative internal states that could generate CRs that are different from taste aversion should not be neglected. Such associations may contribute to the ontogenesis, reinforcement and symptoms of some types of taste- and food-related disorders. We have recently reported that a delayed anxiety-like state, induced by the anxiogenic drug meta-chlorophenylpiperazine (mCPP), can specifically associate with taste to produce CTA. We now show that a similar protocol results in a marked lingering impairment in social interactions in response to the conditioned taste. This is hence a learned situation in which food and company do not mix well.

Topics: Animals; Antimanic Agents; Avoidance Learning; Behavior, Animal; Conditioning, Classical; Food; Interpersonal Relations; Linear Models; Lithium Chloride; Phobic Disorders; Piperazines; Rats; Serotonin Receptor Agonists; Taste

Serotonin(2C) (5-HT(2C)) receptors have been implicated to treat mood disorders such as depression and anxiety. In the present study, the capacities of two 5-HT(2C) agonists, MK212 and mCPP, to produce conditioned taste aversions in mice were evaluated. On two training days, Swiss-Webster male mice (19-34g) were trained to associate the flavor of a novel solution with the injection of various doses of MK212 or mCPP. On two alternate training days, mice were trained to associate a different flavored solution with an injection of saline. For testing, both flavored solutions were presented simultaneously and an avoidance of the MK212 or mCPP-paired solution indicated conditioned taste aversion. Robust conditioned taste aversions were observed to solutions paired with 1.0 or 10mg/kg MK212 or mCPP. Acquisition of conditioned taste aversions was blocked by nonselective serotonin antagonists cyproheptadine, bromo-LSD, metergoline, methysergide and mianserin. Selective 5-HT(2B/2C) antagonist SB206,553 blocked both MK212- and mCPP-induced conditioned taste aversion although selective 5-HT(2B/2C) antagonist SB200,646 only blocked mCPP-induced conditioned taste aversion. In a single-bottle procedure, MK212, bromo-LSD, and mianserin failed to alter acquisition rate of a LiCl-induced conditioned taste aversion. Taken together, these data indicate that the serotonin agonists MK212 and mCPP produce conditioned taste aversion and that these effects are mediated predominantly through 5-HT(2C) receptors.

Topics: Animals; Avoidance Learning; Conditioning, Operant; Cues; Dose-Response Relationship, Drug; Lithium Chloride; Lysergic Acid Diethylamide; Male; Mianserin; Mice; Piperazines; Pyrazines; Receptor, Serotonin, 5-HT2C; Reinforcement, Psychology; Serotonin Antagonists; Taste

The interactions among experience, emotion, and memory are considered to be instrumental in the ontogeny and maintenance of acquired emotional and behavioral disorders (e.g., phobias). Here we address the question whether an anxiety-like state can associate with taste to produce conditioned taste aversion (CTA).. We have used an anxiogenic agent, the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP), to induce an anxiety-like emotional state in rats after consumption of an unfamiliar tastant.. The anxiogenic agent induced CTA. The mCPP-induced CTA could be prevented by concomitant administration of ethanol, which is known to reverse mCPP-induced anxiety-like behavior, at a concentration that had no effect on CTA memory. In contrast, ethanol did not prevent LiCl-induced CTA. Administration of mCPP before the consumption of the tastant had no effect on the preference for that tastant.. Taken together, these results indicate that anxiety-like state can serve as the unconditioned stimulus in CTA training. This finding may be relevant to the ontogeny of pathologies involving food aversion.

Topics: Animals; Anxiety; Avoidance Learning; Behavior, Animal; Central Nervous System Depressants; Conditioning, Psychological; Disease Models, Animal; Drug Interactions; Ethanol; Glycine; Lithium Chloride; Male; Piperazines; Rats; Rats, Wistar; Saccharin; Taste; Time Factors

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

The effect of single and repeated electroconvulsive shock (ECS) (once daily for 7 days) on head twitches produced by 5-HT agonists (LiCl, 5-hydroxytryptophan; 5-HTP and 5-methoxytryptamine; 5-MT) was investigated 1 hr, 24 hr, 5 days and 10 days after the last ECS, while locomotor activity induced by serotonergic agonists (fenfluramine, 3-chlorophenylpiperazine; m-CPP) and antagonists (metergoline, cyproheptadine) was only investigated after 24 hr. 5HT and 5-HIAA concentrations were measured 0.5, 1 and 24 hr after a single ECS and up to 10 days after repeated ECS. Head twitches induced by LiCl were significantly depressed 1 hr after both single and repeated ECS. The number of head twitches produced by LiCl, 5-HTP or 5-MT given 24 hr after single or repeated ECS did not change but it rose significantly 5 and 10 days after the last shock. Repeated ECS increased locomotor activity 24 hr after the last shock. This increase was significantly enhanced by serotonergic antagonists. Biochemical assays showed that a single ECS did not significantly change brain 5-HT and 5-HIAA concentrations 0.5, 1 or 24 hr after the ECS. On the other hand, repeated ECS raised brain 5-HIAA 0.5, 1 and 24 hr or 5 and 10 days and 5-HT 0.5 hr after the final ECS. It is concluded that a single or repeated ECS both depress the serotonergic system response to LiCl but repeated ECS facilitates the response to serotoninomimetics.

Topics: 5-Hydroxytryptophan; 5-Methoxytryptamine; Animals; Brain; Chlorides; Cyproheptadine; Electroshock; Fenfluramine; Lithium; Lithium Chloride; Male; Metergoline; Motor Activity; Piperazines; Rats; Serotonin; Synaptic Transmission