The discriminative stimulus properties of LY233708, a selective serotonin reuptake inhibitor, in the pigeon

Rationale: Understanding the contribution of the various serotonin (5-HT) r eceptor subtypes to the behavioral effects of selective serotonin reuptake inhibitors (SSRIs) may contribute to the discovery of increasingly effectiv e drugs for the treatment of conditions such as depression, panic and obses sive-compulsive disorders. Objectives: A drug discrimination procedure was used to determine whether the administration of an SSRI was associated with a specific interoceptive stimulus cue and to what extent that cue was rela ted to activation of the 5-HT1A receptor. Method: Pigeons were trained to d iscriminate 20 mg/kg of the short acting, SSRI, LY233708 dihydrochloride di hydrate [(-)-cis-1-(6-chloro-1,2,3,4-tetrahydro-1-methyl-2-naphthalenyl)pip erazine] from saline. Results: LY233708 induced a specific, dose-related st imulus cue. The SSRIs, fluoxetine and citalopram, induced dose-related resp onding on the LY233708-associated key. In contrast, nisoxetine, a selective norepinephrine uptake inhibitor, induced responding on the saline-associat ed key. The prototypical 5-HT1A agonist, 8-OH-DPAT [8-hydroxy-(2-di-n-propy lamino)tetralin] substituted for LY233708. This generalization was blocked by the selective 5-HT,A antagonist, WAY-100635 [N-{2-[4-(2-methoxyphenyl)-1 -piperazinyl]ethyl}-N-(2-pyridinyl) cyclohexanecarboxamide]. Conclusion: Th ese data demonstrate that an SSRI can induce a specific, stable discriminat ive stimulus that appears to involve activation of the 5-HT1A receptor in t he pigeon.