THE DISCRIMINATIVE STIMULUS EFFECTS OF METHAMPHETAMINE IN PIGEONS

This experiment was designed to elucidate the neurotransmitter systems that mediate the discriminative stimulus effects of methamphetamine. Four pigeons were trained to peck one key following saline injections and a second key following methamphetamine injections (1.0 or 1.7 mg/k g, IM). Substitution tests revealed drug-appropriate responding follow ing administration of the psychomotor stimulants methamphetamine, amph etamine and cocaine, the dopamine (DA) reuptake inhibitor bupropion, n orepinephrine (NE) reuptake inhibitors imipramine and tomoxetine, and the serotonin (5-HT) releaser fenfluramine. Saline-key responding occu rred following administration of the D-1 agonist SKF-38393, the D-1 an tagonist SCH-23390, the alpha(2) receptor agonist clonidine, the alpha (1)-antagonist prazosin, a nonselective beta-antagonist propranolol an d the selective 5-HT reuptake inhibitor fluoxetine. The D-2/D-3 agonis t quinpirole produced drug-appropriate responding in two pigeons and p artial substitution in the remaining two pigeons. The 5HT(1A) agonist 8-OH-DPAT produced drug-appropriate responding at higher doses (0.3-1. 0 mg/kg), whereas much lower doses (0.003-0.1 mg/kg) antagonized the m ethamphetamine stimulus. The stimulus effects of methamphetamine were attenuated by pretreatment with prazosin, SCH-23390 and eticlopride, w hereas pretreatment with propranolol and the 5-HT3 antagonist, MDL 722 22, failed reliably to attenuate drug key responding. These results su ggest that NE and DA reuptake inhibition and 5-HT release mediate the discriminative stimulus effects of methamphetamine as do the 5-HT1A an d DA D-1 and D-2 receptors.