Differential ability of D1 and D2 dopamine receptor agonists to induce and modulate expression and reinstatement of cocaine place preference in rats.
BACKGROUND
D1-Like agonists are self-administered by drug-naive animals, whereas D2-like agonists reinstate cocaine-seeking behavior, but the rewarding and reinstating effects of D1- and D2-like agonists in pavlovian-based conditioned place preference are equivocal.


OBJECTIVE
To compare the ability of D1 and D2 agonists to produce conditioned place preference with their modulation of expression and reinstatement of an established cocaine place preference.


METHODS
Using an unbiased procedure, we measured the place preference induced by the D1 receptor agonist SKF 81297 and the D2/D3 receptor agonist quinpirole in drug-naive or cocaine-exposed rats. The rewarding effects of the D1 agonists SKF 82958, ABT-431, A-77636, and the D2/D3 receptor agonist 7-OH-DPAT were also tested. Additionally, we tested the ability of SKF 81297 and quinpirole to modulate expression and reinstatement of an established cocaine place preference.


RESULTS
The D1 receptor agonists SKF 81297, SKF 82958, and ABT-431 produced dose-dependent conditioned place preferences, whereas A-77636 produced only place aversion, and the D2/D3 agonists quinpirole and 7-OH-DPAT were without effect in drug naive rats. In cocaine-treated rats, SKF-81297-induced place preference was reduced, whereas quinpirole-induced place preference was revealed. Pretreatment using either D1 or D2/D3 agonists blocked expression of an established cocaine place preference, but only the D1 agonist SKF 81297 and cocaine dose-dependently reinstated an extinguished cocaine place preference, whereas the D2/D3 agonist quinpirole induced place aversion but failed to alter cocaine-induced reinstatement.


CONCLUSIONS
D1, but not D2/D3, agonists mediate rewarding effects and reinstatement of cocaine place preference, but the reinstating effects differ markedly from self-administration paradigms.
Graham
Danielle L
DL
Department of Psychiatry, The Seay Center for Basic and Applied Research in Psychiatric Illness, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9070, USA.
Hoppenot
Regis
R
Hendryx
April
A
Self
David W
DW
D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000523:psychology; D003213:Conditioning, Psychological / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological; D008297:Male; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000378:metabolism; D012201:Reward; D012646:Self Administration
D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D003042:Cocaine