Effects of selective dopamine D1- and D2-agonists and antagonists on timing performance in rats.
Dopamine (DA) D1- and D2-agonists and antagonists were administered at fixed doses to assess putative dopaminergic involvement in timing behavior in rats performing under a peak-interval schedule. Significant shifts in response distributions to the left (consistent with the overestimation of the passage of time) were observed after treatment with the D1- and D2-agonists SKF 38393 and quinpirole, respectively. Both DA antagonists, eticlopride (D2) and SCH 23390 (D1), shifted the response distributions to the right (consistent with the underestimation of the passage of time), but neither drug produced statistically significant shifts. Based on percent shift in peak time from predrug baseline values, no significant differences were detected between agents as a function of their reported affinities for the D1- or D2-receptors. Results indicate the need for a systematic evaluation of each drug at various doses and a more detailed examination of the use of temporal schedules in predicting the efficacy of psychotherapeutic agents.
Frederick
D L
DL
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079-9502, USA. dfrederick@fdant.nctr.fda.gov
Allen
J D
JD
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects*; D019257:Quinpirole; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000037:antagonists & inhibitors*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D012055:Reinforcement Schedule; D012457:Salicylamides / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D004873:Ergolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C045989:eticlopride