Psychopharmacology (1994) 115:173-179 Psychopharmacology © Springer-Verlag 1994 Low doses of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)- tetralin (8-OH DPAT) increase ethanol intake Denise M. Tomkins, Guy A. Higgins, Edward M. Sellers Addiction Research Foundation, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada and Departments of Pharmacology,Medicineand Psychiatry, Universityof Toronto, Toronto, Canada Received: 27 August 1993/Final version: 1 October 1993 Abstract. Previous work has reported that the 5-hydroxy- tryptamine (5-HT)I A agonist, 8-hydroxy 2-(di-n-propy- lamino)tetralin (8-OH DPAT), reduces ethanol intake by rats. However, as 8-OH DPAT reduces 5-HT neurotrans- mission, these findings are inconsistent with the proposed inhibitory role of central 5-HT neurons on ethanol in- take. We examined the effect of 8-OH DPAT on ethanol, water and food intake in rats maintained on a limited access schedule using a lower dose range (6-250 gg/kg) and by assessing concomitant changes in behaviour. Low doses of 8-OH DPAT enhanced ethanol intake even when food and water were offered as alternatives. Sup- pression in ethanol intake was observed at higher doses where elements of the 5-HT syndrome were apparent. Similar observations were made in both fluid and non- fluid deprived water drinking rats, suggesting the latter effect is non-selective. Therefore 8-OH DPAT may both increase or decrease ethanol consumption in the rat de- pending on the dose used. Key words" Limited access schedule - Ethanol intake - 8-OH DPAT - Behaviour - 5-HT - Water deprivation The highly selective 5-HTaA receptor agonist, 8-hydroxy- 2-(di-n-propylamino)-tetralin (8-OH DPAT), reliably in- creases feeding in rats (Dourish et al. 1985a, b; Fletcher 1987; Shepherd and Rodgers 1990). Initially, these find- ings seemed contradictory to the accepted role of 5-HT in feeding, because in general, enhancement of 5-HT function such as by selective 5-HT reuptake inhibitors or 5-HT releasers, attenuates this behaviour (Lucki et al. 1988; Neill and Cooper 1989). This anomaly has since been reconciled by the observation that 8-OH DPAT stimulates feeding via a direct activation of the inhibito- ry somatodendritic 5-HT1A autoreceptor, localised on Correspondence to: D.M. Tomkins, Addiction Research Founda- tion, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada the dorsal and median raphe nuclei (DRN, MRN), the consequence of which is a reduction of 5-HT neu- rotransmission to areas innervated by either raphe nucle- us (Bendotti and Samanin 1986; Hutson etat. 1986; Fletcher and Davies 1990). Therefore 8-OH DPAT-in- creased feeding is probably due to a reduction in central 5-HT function (Hjorth and Sharp 1991). In addition to somatodendritic 5-HTIA receptors, postsynaptic 5-HT1A receptors also exist, and these are localised in a number of brain regions, such as the hippocampus (Miquel et al. 1991). Stimulation of postsynaptic 5-HT1A receptors, which may require higher concentrations of 8-OH DPAT, elicits behaviours reflective of enhanced 5-HT activity, including the 5-HT syndrome (Smith and Per- outka 1986). Enhanced central 5-HT function has also been dem- onstrated to attenuate ethanol intake and preference in rats, primates and man (Mc Bride et al. 1990; Higgins et al. 1992; Sellers et al. 1992). In contrast, increases in alcohol intake/preference following treatments that re- duce 5-HT functioning are inconsistent (Sellers et al. 1992), although certain alcohol preferring strains of rat (e.g. alcohol P, Fawn hooded, HAD line) show neu- rochemical markers indicative of lower 5-HT levels rela- tive to their lower alcohol preferring counterparts (Mur- phy et al. 1987a; Gongwer et al. 1989; Mc Bride et al. 1990; Overstreet et al. 1992). These findings suggest that low doses of 8-OH DPAT, which have been shown to reduce 5-HT neurotransmission via activation of soma- todendritic 5-HT1A autoreceptors, may enhance volun- tary ethanol intake in a manner analogous to feeding. A limited number of studies have investigated the effects of 8-OH DPAT on voluntary ethanol intake and in gen- eral they report a decrease in consumption (Svensson et al. 1989; McBride et al. 1990; Kostowski and Dyr 1992). However, the doses used have been comparatively high and would almost certainly elicit elements of the 5-HT syndrome which may be incompatible with etha- nol drinking (Smith and Peroutka 1986). Since behav- iour was not formally measured in these studies, this possibility has not been specifically addressed.