Involvement of dopamine D3 and D4 receptors in the discriminative stimulus properties of cocaine in the rat.
The present study was carried out to determine the involvement of dopamine receptor subtypes D3 and D4, in the discriminative stimulus effects of cocaine in the rats trained to discriminate 10 mg/kg of cocaine from vehicle. The discriminative stimulus effects of cocaine (1-10 mg/kg) were dose-dependent. The dopamine D2 receptor agonist bromocriptine (1.25-20 mg/kg) and the dopamine D3 receptor agonist R(+)-7-OH-DPAT (0.0001-0.3 mg/kg) produced cocaine (10 mg/kg)-like discriminative stimulus effects. Both the dopamine D3 receptor antagonist GR103691 (1 mg/kg) and the dopamine D4 receptor antagonist L745870 (1 mg/kg) partially antagonized the discriminative stimulus effects of cocaine (10 mg/kg) and the cocaine (10 mg/kg)-like discriminative stimulus effects of R(+)-7-OH-DPAT (0.3 mg/kg). L745870 (0.001 mg/kg) inhibited the antagonistic effects of GR103691 (1 mg/kg) on the discriminative stimulus effects of cocaine (10 mg/kg), whereas the drug (0.001 mg/kg) enhanced the antagonistic effects of GR103691 (1 mg/kg) on the cocaine (10 mg/kg)-like discriminative stimulus effects of R(+)-7-OH-DPAT (0.3 mg/kg). GR103691 (1 mg/kg) in combination with L745870 (0.001 mg/kg) did not markedly affect the cocaine (10 mg/kg)-like discriminative stimulus effects of bromocriptine (20 mg/kg). These results suggest that the discriminative stimulus effects of cocaine are different from the cocaine-like discriminative stimulus effects of bromocriptine or R(+)-7-OH-DPAT, in terms of dopamine D3 and D4 receptors.
Ukai
M
M
Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan. ukai@ccmfs.meijo-u.ac.jp
Mitsunaga
H
H
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001971:Bromocriptine / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors; D050638:Receptors, Dopamine D4 / Q000037:antagonists & inhibitors; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
C099630:3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine; D001713:Biphenyl Compounds; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D011725:Pyridines; D011758:Pyrroles; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C105771:GR 103691; D050638:Receptors, Dopamine D4; D001971:Bromocriptine; D003042:Cocaine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin