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There is growing evidence to show that atypical antipsychotic quetiapine might exert an anxiolytic effect in patients. Nevertheless, the mechanism underlying this effect has not yet been fully explored. Like other anxiolytic drugs, quetiapine exhibits partial agonistic activity toward serotonergic 1A (5HT1A) receptors. The involvement of the serotonin system in anxiety, particularly of 5HT1A receptors, has been widely documented. In this study we have investigated whether different doses of quetiapine (5, 10, and 30 mg/kg, oral gavage) administered to C57BL6/N mice could produce an anxiolytic effect in the Vogel conflict test, a classical model of anxiety, and whether or not the selective 5HT1A antagonist WAY100635 (0.1 mg/kg, subcutaneously) might prevent such an effect. Our results show that 10 mg/kg quetiapine exhibits an anxiolytic effect, that is, at least in part, 5HT1A-mediated, because it is completely eliminated by WAY100635.

Rationale: The anxiolytic effect of ethanol is generally considered to be causally related to the development of alcohol dependence, and serotonin (5-HT) has been involved in both alcohol abuse and anxiety disorders. Several lines of evidence suggest an inverse relationship between alcohol abuse and central serotonergic neurotransmission., Objectives: When tested in the elevated plus-maze, selectively bred Sardinian alcohol-preferring (sP) rats display a higher degree of anxiety than Sardinian alcohol-non-preferring rats (sNP); this behavior is reversed by voluntary ethanol intake. The present study examined whether sP rats differed with respect to the 5-HT innervation in different forebrain areas., Methods: We performed an immunohistochemistry study using an antibody raised against serotonin transporter (SERT), a marker for 5-HT fibers, coupled with an unbiased stereology, the method used to count the number of 5-HT neurons in the raphe nuclei., Results: The SERT-positive innervation density was found to be significantly lower in the medial-prefrontal cortex and in the shell of the nucleus accumbens of the ethanol-naive sP rats (sP-N) when compared with the sNP and unselected Wistar rats. No differences were found in the caudate putamen and hippocampus. The stereological analysis showed a significant difference in the number of 5-HT neurons in the dorsal but not in the median raphe of sP-N rats, compared with sNP and Wistar rats. Analysis of the cell body cross-sectional area revealed no differences among the three lines of rats either in the dorsal or in the median raphe. In sP rats that had voluntarily drunk ethanol for 14 consecutive days (sP-exp), no differences were found in the 5-HT innervation relative to sP-N animals., Conclusions: These results indicate a selective reduction of innervation in the medial portion of the mesocorticolimbic 5-HT system in sP rats, suggesting that this genetically determined difference may be involved in the contrasting alcohol preference and consumption of sP and sNP animals.