Role of dopamine D2 and D3 receptors in mediating the U-50,488H discriminative cue: comparison with methamphetamine and cocaine.

Kazumi Yoshizawa, Minoru Narita, Tomohisa Mori, Mayumi Miyatake, Kana Isotani, Shiro Tomiyasu, Yoshi Tsukiyama, Tsutomu Suzuki

Index: Addict. Biol. 17(6) , 949-55, (2012)

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Abstract

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.© 2010 The Authors, Addiction Biology © 2010 Society for the Study of Addiction.