Reward summation and the effects of dopamine D1 and D2 agonists and antagonists on fixed-interval responding for brain stimulation.
The effects of dopamine D1 and D2 agonists and antagonists on fixed-interval (FI) self-stimulation were investigated using a reward-summation model, trading off frequency with train duration. The D1 antagonist SCH 23390 (0.005-0.02 mg/kg) decreased FI self-stimulation and the inhibition was reversed by increasing stimulation frequency. Moreover, amphetamine (0.5 mg/kg) reversed the inhibition by a low dose of SCH 23390 (0.005 mg/kg) but not after a higher dose inhibition could not be dissociated from a performance deficit. There was no significant interaction between low doses of spiperone and SCH 23390 when coadministered that could not be predicted from their effects when given individually. Self-stimulation was inhibited by the D1 agonist SKF 38393 (5 mg/kg). When coadministered with amphetamine, SKF 38393 partially blocked amphetamine's facilitation. The D2 agonist bromocriptine (10 mg/kg) produced an extraordinary enhancement of performance that was also evident after a lower dose (5 mg/kg) when it was combined with amphetamine. This enhancement of performance showed little extinction when stimulation was no longer available, suggesting it was a novel form of stereotypy. These results support the concept that D1 dopamine receptors play a critical role in modulating the reinforcing consequences of lateral hypothalamic stimulation. The involvement of D2 receptors on reinforcement processes remains contentious due to their effects on performance and insensitivity of responding to coincide with changes in reinforcement magnitude.
Department of Psychiatry, University of Sydney, New South Wales, Australia.
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Hunt
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Atrens
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Jackson
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000502:physiology*; D001971:Bromocriptine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D065127:Dopamine D2 Receptor Antagonists; D004347:Drug Interactions; D004558:Electric Stimulation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000037:antagonists & inhibitors*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D012055:Reinforcement Schedule; D012201:Reward; D012653:Self Stimulation; D013134:Spiperone / Q000494:pharmacology
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D013134:Spiperone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000661:Amphetamine