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

Authors


Minoru Narita and Tsutomu Suzuki, Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. E-mail: narita@hoshi.ac.jp; suzuki@hoshi.ac.jp

ABSTRACT

Substitutions of the dopamine D2 or D3 receptor agonists for the discriminative stimulus effect induced by U-50,488H, methamphetamine (METH) and cocaine in rats were examined. The D2 receptor agonist R-propylnorapomorphine [(−)-NPA] failed to substitute for U-50,488H cue, while the D3 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 D2 receptors. These results suggest that the stimulation of D2 receptor may be critical for the production of the discriminative stimulus effect induced by METH and cocaine, whereas the stimulation of D3 receptor may contribute to the production of the U-50,488H cue.

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