DISSOCIATION OF SEROTONERGIC REGULATION OF ANXIETY AND ETHANOL SELF-ADMINISTRATION - A STUDY WITH MCPP

Alcohol dependence frequently co-exists with anxiety disorders, althou gh it is unclear how these disorders functionally or neurochemically r elate. Central serotonergic dysfunction may be one common factor. The aim of this study was to compare the effects of the mixed 5-HT agonist m-chlorophenylpiperazine (mCPP) on both anxiety-related (hole board/p lus maze) and ethanol self-administration (limited access procedure) b ehaviours in male Wistar rats. mCPP was selected because it is known t o be anxiogenic in both animals and humans, and to induce ''craving'' in abstinent alcoholics. For comparative purposes pentylenetetrazole ( PTZ), a non-serotonergic anxiogenic agent, was also examined. mCPP (0. 3 and 1.0 mg/kg s.c.) decreased exploratory behaviour in both the hole board and plus maze, which is indicative of anxiogenesis. At comparab le doses, mCPP reduced ethanol and water intake during a Limited acces s procedure where rats were presented with both a 12% ethanol solution and water. mCPP-induced anxiogenesis was reversed by two antagonists, metergoline (5-HT1/2 receptor antagonist) and ritanserin (5-HT2A/2C r eceptor antagonist). However, the effect of mCPP on ethanol was modifi ed only by metergoline, which suggests that different 5-HT receptor su btypes are involved in regulating these behaviours. Furthermore, there was no evidence of tolerance to the anxiogenic effect of mCPP (0.3 mg /kg) following chronic (8 days) treatment. However, tolerance develope d to its effect on ethanol intake. Upon discontinuation ethanol intake increased (by 41%). In contrast, PTZ (15.0 mg/kg i.p.) induced anxiog enesis in the plus maze and also increased ethanol intake on chronic a dministration. Since mCPP and PTZ had opposite effects on ethanol inta ke, the effect of mCPP may not be related to its anxiogenic properties but rather reflect its non-selective pharmacology. This non-selectivi ty of mCPP makes it an unsatisfactory pharmacological tool with which to investigate the functional relationship between anxiety and alcohol dependence.