A dopamine D1 agonist elevates self-stimulation thresholds: comparison to other dopamine-selective drugs.
The effects of the high-efficacy D1 receptor agonist SKF 81297 and the D2/3 receptor agonist 7-OH-DPAT on brain stimulation reward thresholds and on response latencies in responding for the stimulation, were compared to the effects of subtype-selective receptor antagonists and a dopamine uptake blocker. SKF 81297 produced dose-dependent elevations in reward thresholds but did not alter response latencies. In contrast, 7-OH-DPAT produced inconsistent reward threshold elevations, yet dose dependently increased response latencies. Both the dopamine D1 receptor antagonist SCH 23390 and the D2 antagonist raclopride elevated reward thresholds, but only raclopride significantly increased response latencies. The dopamine uptake inhibitor GBR 12909 lowered reward thresholds and did not influence response latencies. The present results provide a clear demonstration that a selective, high-efficacy D1 receptor agonist elevates brain stimulation reward thresholds without producing performance deficits. Furthermore, it was observed that the effects upon reward measures of D1-selective compounds, but not D2/D3-selective compounds, are dissociable from their effects upon response latency in this task. These results are discussed with regard to a distinction between the effects of indirect and direct dopamine agonists on reward thresholds, a distinction that does not depend upon the subtype-selectivity of the direct agonists tested.
Baldo
B A
BA
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jain
K
K
Veraldi
L
L
Koob
G F
GF
Markou
A
A
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004567:Electrodes, Implanted; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects*
D001552:Benzazepines; D015259:Dopamine Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; C067113:SK&F 81297