title: D4 dopamine receptor-specific antagonist improves reversal learning impairment in amphetamine-treated male rats.
abstract: The Attentional Set-Shifting Task (ASST) is a rodent analog of the Wisconsin Card Sorting Task, which measures executive functioning. The ASST tests for reversal of stimulus-response learning and the formation and maintenance of attentional sets. Depletion of dopamine has been shown to improve performance on attentional shifts. The study presented here questioned whether a D₄-specific antagonist, L-745,870, could have a similar effect on animals, even after being treated with repeated doses of amphetamine. Three groups of male rats were given either 10 saline injections (n = 12), 10 amphetamine injections (2 mg/kg; n = 8), or 10 amphetamine injections plus 1 pretreatment injection of L-745,870 (0.1 mg/kg; n = 8) 20 min prior to testing. One-way ANOVA results showed that amphetamine-only rats were impaired on all 3 reversals (Ms = 19, 16.4, and 17.1) compared with L-745,870-treated rats (Ms = 9.8, 10.9, and 9.6) and controls (Ms = 8.6, 9.6, 9.3; all ps < .01). L-745,870-treated rats also displayed reduced latencies to respond compared with both saline controls and amphetamine rats. It is thought that D₄ receptors play a role in cue salience, and that by blocking these receptors, animals display less attachment to previously rewarded cues. The results presented support this idea and imply that blocking of D₄ receptors can reverse the impairment in reversals caused by amphetamine.
authors.affiliation: Department of Psychology, American University.
authors.forename: Nina P
authors.initials: NP
authors.lastname: Connolly
authors.affiliation: Department of Psychology, American University.
authors.forename: Maria
authors.initials: M
authors.lastname: Gomez-Serrano
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000633:toxicity*; D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001288:Attention / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity; D003463:Cues; D018492:Dopamine Antagonists / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D056344:Executive Function / Q000187:drug effects; D007859:Learning Disabilities / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D058990:Molecular Targeted Therapy; D018697:Nootropic Agents / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D020318:Rats, Long-Evans; D050638:Receptors, Dopamine D4 / Q000037:antagonists & inhibitors*; D012193:Reversal Learning / Q000187:drug effects*; D012201:Reward; D012720:Severity of Illness Index
chemical_list: C099630:3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D018697:Nootropic Agents; D011725:Pyridines; D011758:Pyrroles; D050638:Receptors, Dopamine D4; D000661:Amphetamine