Dopamine D2/D3 receptor agonist quinpirole impairs spatial reversal learning in rats: investigation of D3 receptor involvement in persistent behavior.
BACKGROUND
Dopamine is strongly implicated in the ability to shift behavior in response to changing stimulus-reward contingencies.


OBJECTIVE
We investigated the effects of systemic administration of the D2/D3 receptor agonist quinpirole (0.1, 0.3 mg/kg), the D2/D3 receptor antagonist raclopride (0.1, 0.3 mg/kg), the selective D3 antagonist nafadotride (0.3, 1.0 mg/kg), and combined administration of raclopride (0.1 mg/kg) or nafadotride (1.0 mg/kg) with quinpirole (0.3 mg/kg) on spatial discrimination and reversal learning.


METHODS
Rats were trained on an instrumental two-lever spatial discrimination and reversal learning task. Both levers were presented, only one of which was reinforced. The rat was required to respond on the reinforced lever under a fixed ratio 3 schedule of reinforcement. Following attainment of criterion, a reversal was introduced.


RESULTS
None of the drugs altered performance during retention of the previously reinforced contingencies. Quinpirole (0.3 mg/kg) significantly impaired reversal learning by increasing both trials and incorrect responses to criterion in reversal phase, a pattern of behavior manifested as increased perseverative responding on the previously reinforced lever. In contrast, neither raclopride nor nafadotride when administered alone altered reversal performance. However, raclopride blocked the quinpirole-induced reversal deficit, whereas combined administration of nafadotride and quinpirole affected not only performance during the reversal but also the retention phase. The reversal impairment resulting from co-administration of nafadotride and quinpirole was associated with both perseverative and learning errors.


CONCLUSIONS
Our data indicate distinct roles for D2 and D3 receptors in the capacity to modify behavior flexibly in the face of environmental change.
Boulougouris
Vasileios
V
Department of Experimental Psychology, Behavioral and Clinical Neuroscience Institute (BCNI), University of Cambridge, Downing Street, CB23EB Cambridge, UK. vb257@cam.ac.uk
Castañé
Anna
A
Robbins
Trevor W
TW
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D019257:Quinpirole / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3 / Q000819:agonists* / Q000037:antagonists & inhibitors; D012193:Reversal Learning / Q000187:drug effects*; D012691:Serial Learning / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D009281:Naphthalenes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D019257:Quinpirole; D020891:Raclopride; C097285:nafadotride