Preferential involvement of D3 versus D2 dopamine receptors in the effects of dopamine receptor ligands on oral ethanol self-administration in rats.
There is evidence that dopamine transmission is involved in reinforcement processes and the present study investigated the relative involvement of D3 versus D2 dopamine receptors in the effects of dopamine ligands on the reinforcing action of ethanol. Rats were trained to self-administer ethanol (10% v/v) orally in a free-choice two-lever operant task using a saccharin-fading procedure. When preference in responding for ethanol over water had developed the rats were tested with several dopamine agonists and antagonists. Pretreatment with the non-selective dopamine agonist, apomorphine (0.01-0.1 mg/kg), the preferential D2 agonist, bromocriptine (1-10 mg/kg) and the selective D3 agonists, 7-OH-DPAT (0.003-0.1 mg/kg), PD 128907 (0.1-3 mg/kg), (+)3PPP (0.3-3 mg/kg), quinelorane (0.0001-0.003 mg/kg) and quinpirole (0.003-0.03 mg/kg), resulted in dose-dependent decreases in responding for ethanol. The relative potencies of the dopamine agonists to decrease ethanol self-administration were highly correlated with their published potencies to produce in vitro functional D3 but not D2 responses. Active doses could be considered as those selectively stimulating receptors involved in the control of dopamine release, suggesting that reduction of dopamine transmission was associated with a decrease in ethanol-reinforced responding. This conclusion was further supported by the finding that pretreatment with the D2/D3 dopamine antagonists, haloperidol (0.1-0.4 mg/kg) and tiapride (10-60 mg/kg), decreased responding for ethanol at doses which have been shown previously to block dopamine transmission.
Cohen
C
C
Synthelabo Recherche, Bagneux, France.
Perrault
G
G
Sanger
D J
DJ
D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D050637:Receptors, Dopamine D3; D013976:Tiapamil Hydrochloride / Q000494:pharmacology
D015259:Dopamine Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C493595:Drd3 protein, rat; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D006220:Haloperidol; D013976:Tiapamil Hydrochloride