Dopamine D1 and D2 antagonist effects on response likelihood and duration.
Experimentally induced and parkinsonian disruptions in dopamine (DA) transmission are associated with motor abnormalities that include a reduced likelihood of behavioral response initiation and an increased duration of executed responses. Here we investigated the dopamine receptor subtypes involved in regulating these two aspects of behavior. We examined the effects of D1 family (D1/D5) antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390; 0, 0.04, 0.08, or 0.16 mg/kg) and D2/D3 antagonist 3,5-dichloro-N-(1-ethylpyrrolidin-2-ylmethyl)-2-hydroxy-6-methoxybenzamide (+)-tartrate salt (raclopride; 0, 0.2, or 0.4 mg/kg) on the likelihood and duration of a cued Pavlovian approach and a cued operant lever-press response. While the high doses of the D1 and D2 antagonists produced similar levels of overall locomotor suppression, only the D2 antagonist increased the duration of time that animals' heads remained in the food compartment during both Pavlovian and operant task performance. In contrast, D1 antagonist SCH23390 decreased the proportion of trials in which animals executed both the Pavlovian approach and operant lever-press, while raclopride did not. The results suggest that D2 receptor blockade preferentially increases response duration, and, under the simple discrete-trial procedures employed here, D1 receptor blockade preferential reduces Pavlovian and operant response likelihood.
Choi
Won Yung
WY
Columbia University, Department of Psychiatry, New York, New York, USA.
Morvan
Cecile
C
Balsam
Peter D
PD
Horvitz
Jon C
JC
D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage; D003214:Conditioning, Classical / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D018492:Dopamine Antagonists / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D020891:Raclopride / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*
D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D020891:Raclopride