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Role of dopamine D 2 and D 3 receptors in mediating the U‐50,488H discriminative cue: comparison with methamphetamine and cocaine
Author(s) -
Yoshizawa Kazumi,
Narita Minoru,
Mori Tomohisa,
Miyatake Mayumi,
Isotani Kana,
Tomiyasu Shiro,
Tsukiyama Yoshi,
Suzuki Tsutomu
Publication year - 2012
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/j.1369-1600.2010.00257.x
Subject(s) - agonist , chemistry , methamphetamine , pharmacology , receptor , stimulus control , hydrobromide , stimulation , endocrinology , medicine , biochemistry , nicotine
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.