Activation of serotonin (5-HT)(1A) receptors inhibits amphetamine sensitization in mice

The effects of serotonin (5-HT)(1A) drugs on the development and expression of sensitization to the locomotor effect of amphetamine (AMPH) were studie d in mice. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A ago nist, dose-dependently reduced the expression of AMPH (2.5 mg/kg)-induced s ensitization. The latter inhibitory effect of 8-OH-DPAT was reversed by (S) -N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropamine (WAY 100135), a 5-HT1A antagonist. WAY 100135 given alone did not affect express ion of AMPH sensitization. Combined injections of 8-OH-DPAT, but not WAY 10 0135, with AMPH (2.5 mg/kg) during the development of sensitization, protec ted against the expression of sensitization to a challenge dose of AMPH (2. 5 mg/kg) 3 days after withdrawal. The above inhibitory effect of 8-OH-DPAT on the development of AMPH sensitization was blocked by pretreatment with W AY 100135. The AMPH-induced conditioned locomotion was unaffected by pretre atment with 8-OH-DPAT. These results indicate that 5-HT1A receptors are not involved in AMPH-induced sensitization per-se, whereas their pharmacologic al activation leads to the inhibition of both the development and the expre ssion of AMPH-induced sensitization.