Reevaluation of PNU-99194A discriminative stimulus effects: potentiation by both a D2 antagonist and a D3/D2 agonist.
This study evaluated the relative importance of D(3) receptor antagonism in the discriminative stimulus effects of the putative D(3) receptor antagonist PNU-99194A. Eight male Sprague-Dawley rats were trained to discriminate PNU-99194A (10 mg/kg sc) from vehicle in a two-choice drug discrimination procedure under a FR 20 schedule of food reinforcement. The selective D(3) antagonists PD 152255 and S14297 were examined for stimulus generalization. The D(2) antagonist haloperidol and the D(2)/D(3) receptor agonist (+)-7-OH-DPAT were also assessed for antagonism of PNU-99194A discrimination. PD 152255 (1.0-3.0 mg/kg) engendered no generalization to PNU-99194A. Due to its markedly rate-suppressive effects, PD 152255 could not be tested at higher doses. S-14297 produced partial substitution (66%) for PNU-99194A at both 3.0 and 8.0 mg/kg. Neither haloperidol nor (+)-7-OH-DPAT blocked the discrimination of PNU-99194A and, surprisingly, actually appeared to potentiate its effects. These data, along with other recent findings, suggest that the discriminative stimulus effects of PNU-99194A appear to involve complex pharmacological actions and are not solely mediated by D(3) receptor antagonism.
Baker
Lisa E
LE
Department of Psychology, Western Michigan University, Kalamazoo, MI 49008, USA. lisa.baker@wmich.edu
Prus
Adam J
AJ
D000818:Animals; D004192:Discrimination, Psychological / Q000187:drug effects* / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004357:Drug Synergism; D007189:Indans / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000502:physiology; D050637:Receptors, Dopamine D3
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D007189:Indans; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C086335:(5,6-dimethoxyindan-2-yl)dipropylamine