AN ETHOPHARMACOLOGICAL ANALYSIS OF SELECTIVE ACTIVATION OF 5-HT1A RECEPTORS - THE MOUSE 5-HT1A SYNDROME

The behavioral effects of 8-OH-DPAT [0.5-10 mg/kg intraperitoneally (I P)] and (+) S-20499 (1-20 mg/kg IF), a recently synthesized 5-HT1A rec eptor full agonist, were examined over a 2-h period in mice in a neutr al cage and, during the peak period of effect, in a runway. 8-OH-DPAT (1 and 10 mg/kg) and (+) S-20499 (10 and 20 mg/kg) blocked vertical ac tivity (i.e., rearing and hanging on the wire mesh) during the period postinjection when levels of activity of the control mice were high. I n this initial period (0-30 min), mice treated with 8-OH-DPAT, but not those treated with (+) S-20499, displayed flat back rather than curve back locomotion (0.5-10 mg/kg). However, after about 50 min, marked h yperactivity emerged for 8-OH-DPAT at 0.5 and 1 mg/kg and for (+) S-20 499 at all doses, including increases in rearing, hanging, grooming. a nd, for (+) S-20499, curve back locomotion. Both 8-OH-DPAT (10 mg/kg) and (+) S-20499 (>20 mg/kg) significantly enhanced eating responses. B oth drugs rapidly induced straub tail responses at all doses, and this effect remained significant until the end of the experiment at the hi ghest doses. Subjects treated with 0.5 mg/kg of 8-OH-DPAT and 10 mg/kg of (+) S-20499 displayed in the initial time period ''ballistic-type' ' rapid forelimb movements targeted toward the side of the head. Durin g peak drug effect periods, higher doses of both drugs produced signif icant increases in movement with a change of direction, including rota tion around the hindlimbs, suggesting, as do the ballistic-type moveme nts, particular involvement of the forelimbs. These findings provide e vidence consonant with the view that selective activation of 5-HT1A re ceptors in mice produces distinct behavioral changes in part associate d with the 5-HT syndrome. Moreover, these changes differ, in the speci fic movements induced and in the drug parameters and time course of ch anges, from those reported in the laboratory rat. (C) 1997 Elsevier Sc ience Inc.