Prior repeated exposure to a 5-HT3 receptor agonist does not alter the ethanol-induced conditioned taste aversion in rats.

Several reports have indicated that the brain serotonergic 5-HT3 receptors are involved in at least some central effects of ethanol in rats. However, using an operant drug discrimination procedure, we have shown that these receptors are not primarily involved in the discriminative stimulus effects of ethanol. The aim of the present study was to further elucidate the role of 5-HT3 receptors in the formation of the ethanol-cueing effects in rats. To this purpose, a crossfamiliarization conditioned taste aversion (CF-CTA) procedure was used. Four daily injections of 1.5 g/kg ethanol (10% v/v) resulted in a significant attenuation of the subsequent ethanol-induced CTA. In contrast, four daily injections of the 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide (mCPBG; 50 microg per rat, i.c.v.) did not alter the subsequent ethanol-induced CTA. The 50 microg dose of mCPBG produced a marked CTA in a control experiment. These results taken together with some previous findings from our laboratory suggest that the brain 5-HT3 receptors do not play any crucial role in the mediation of the discriminative stimulus effects of ethanol.

5,7-dihydroxytryptamine lesion does not affect ethanol-induced conditioned taste and place aversion in rats.

The effect of the lesion of central serotonergic neurons by 5,7-dihydroxytryptamine (5,7-DHT), on ethanol-induced taste and place aversion conditioning was studied in male Wistar rats. Control biochemical analysis revealed that 5,7-DHT (250 micrograms per rat, free base, i.c.v.) produced marked and selective depletion of serotonin (5-HT) in the hippocampal formation and the limbic forebrain complex. Ethanol-induced (1.5 g/kg, i.p.) conditioned taste aversion (CTA) to saccharin solution was unaffected by the lesion of central serotonergic neurons. The 5,7-DHT-lesioned and sham-lesioned rats showed comparable ethanol-induced CTA even 30 days after the last ethanol injection. Similarly, ethanol-induced (1.5 g/kg, i.p.) conditioned place aversion (CPA) was unaffected by 5,7-DHT administration. These results suggest that central serotonergic pathways are not primarily involved in the aversive effects of high ethanol doses in rats.

Discriminative stimulus properties of ethanol in the rat: differential effects of selective and nonselective benzodiazepine receptor agonists.

Rats were trained to discriminate between ethanol (1.0 g/kg; 10% v/v) and saline under a fixed ratio 10 schedule of sweetened milk reinforcement. Both diazepam [nonselective, full benzodiazepine (BZ) receptors agonist] and bretazenil (nonselective, partial BZ receptor agonist) produced dose-dependent ethanol-appropriate responding (>75%). Neither diazepam nor bretazenil affected the response rate at the doses producing maximal generalisation from ethanol. In contrast, zolpidem (full BZ1 receptor agonist) and abecarnil (full BZ1/full or partial BZ2 receptor agonist) produced only moderate (<50%) ethanol-appropriate responding when tested up to doses that markedly decreased the overall response rate. These results suggest that: 1) there are no major differences between full and partial, nonselective BZ receptor agonists in their ability to substitute for 1.0 g/kg dose of ethanol; 2) stimulation of BZ1 receptors alone is not sufficient to produce ethanol-like discriminative stimulus effects in the rat.