Role of 5-HT1B receptors in the sensitization to amphetamine in mice

The present study was designed to determine how 5-HT1B receptor ligands aff ected the development or the expression phase of sensitization to the amphe tamine-induced locomotor response in mice. Mice were treated repeatedly (fo r 5 days) with amphetamine (2.5 mg/kg) in combination with either vehicle, N-[3-[3-(dimethylamino)ethoxy]-4-methoxyphenyl]-2'-methyl-4'-(5-methyl-1.2, 4-oxadiazol-3yl)-[1, 1'-biphenyl]-4-carboxamide hydrochloride (SB 216641; a n antagonist of 5-HT1B receptors), 3-(1,2.5,6-tetrahydro-4-pyridyl)-5-propo xypyrrolo[3,2-b]pyridine (CP 94,253, an agonist of 5-HT1B receptors), or SB 216641 + CP 94,253; afterwards, on day 10, they received a challenge dose of amphetamine (2.5 mg/kg). In another experiment, mice were given either v ehicle or amphetamine (2.5 mg/kg) for 5 days, and were then challenged with amphetamine (2.5 mg/kg) in combination with vehicle, SB 216641, or CP 94.2 53 on day 10. Locomotor hyperactivity induced by acute administration of am phetamine(day 1) was dose-dependently inhibited by SB 216641 and enhanced b y CP 94,253, but not affected by a combination of SB 216641 + CP 94,253. Th e 5-HT1B receptor ligands affected similarly the behavioral response to the challenge dose of amphetamine on day 10 (ca. 55-110% more potent than the response to its first administration) when they were combined with the psyc hostimulant during the development phase (days 1-5) of sensitization. On th e other hand, neither SB 216641 nor CP 94,253 administered together with th e challenge dose of amphetamine (day 10) affected its behavioral hyperactiv ity effect in mice treated repeatedly (days 1-5) with the psychostimulant a lone. Our results suggest that 5-HT1B receptors may play a permissive role in the development, but not expression, of behavioral sensitization, as wel l as in the acute locomotor response to amphetamine in mice. (C) 2001 Elsev ier Science B.V. All rights reserved.