Role of dopamine D2 and D3 receptors in mediating the U-50,488H discriminative cue: comparison with methamphetamine and cocaine.
Substitutions of the dopamine D(2) or D(3) receptor agonists for the discriminative stimulus effect induced by U-50,488H, methamphetamine (METH) and cocaine in rats were examined. The D(2) receptor agonist R-propylnorapomorphine [(-)-NPA] failed to substitute for U-50,488H cue, while the D(3) receptor-preferred agonist (+/-)-7-hydroxy-dipropylaminotetralin hydrobromide (7-OH-DPAT) produced dose-related increases in drug-appropriate responding up to 0.03 mg/kg, which fully substituted. At doses greater than 0.03 mg/kg of 7-OH-DPAT, there was a dose-dependent decrease in the percentage of responses on the U-50,488H-appropriate lever. Furthermore (-)-NPA and 7-OH-DPAT at high doses substituted for the discriminative stimulus effect induced by both METH and cocaine, indicating that 7-OH-DPAT at high doses may interact with D(2) receptors. These results suggest that the stimulation of D(2) receptor may be critical for the production of the discriminative stimulus effect induced by METH and cocaine, whereas the stimulation of D(3) receptor may contribute to the production of the U-50,488H cue.
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Japan.
Kazumi
K
Yoshizawa
Minoru
M
Narita
Tomohisa
T
Mori
Mayumi
M
Miyatake
Kana
K
Isotani
Shiro
S
Tomiyasu
Yoshi
Y
Tsukiyama
Tsutomu
T
Suzuki
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000187:drug effects*; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
C425777:10,11-dihydroxy-N-n-propylnorapomorphine; D018712:Analgesics, Non-Narcotic; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; C493595:Drd3 protein, rat; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D008694:Methamphetamine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D003042:Cocaine; D001058:Apomorphine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin