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Brain Res. 1996 Apr 15;716(1-2):107-17.

Differences among mouse strains in the regulation by mu, delta 1 and delta 2 opioid receptors of striatal adenylyl cyclases activated by dopamine D1 or adenosine A2a receptors.

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Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA.


It is well established that the intensity of the morphine-induced locomotor stimulatory response in rodents is genetically determined. We have evaluated the ability of mu (DAMGO). delta 1 (DPDPE) and delta 2 ([D-Ala2]deltorphin II; DT-II) selective opioid receptor agonists to inhibit receptor-activated adenylyl cyclase activity. Previous studies have shown that dopamine D1 receptors are preferentially expressed in striatonigral neurons, while adenosine A2a receptors are preferentially expressed in striatopallidal neurons. Our results indicate that in striatum of wild-type CD1 mice as in rat. mu-agonists inhibit D1-activated adenylyl cyclase, but were without inhibitory activity against A2a-activated adenylyl cyclase. In all tested mouse strains, the delta 1 selective agonist, DPDPE, inhibited the A2a-activated adenylyl cyclase but not the D1-activated enzyme. In contrast, the delta 2 agonist, DT-II, inhibited both D1 and A2a activated enzyme in all strains except DBA/2J, where DT-II did not inhibit D1-activated adenylyl cyclase. In C57BL/6J mice, which are highly sensitive to morphine-induced motor stimulation, mu agonists were potent inhibitors of A2a-activated adenylyl cyclase but did not inhibit the D1-activated enzyme, while mu opioids did not inhibit A2a-activated enzyme in DBA/2J mice which show little locomotor response to morphine. In CXBK mice, a strain with known deficiencies in mu-receptor expression, both forms of receptor-activated adenylyl cyclase were less sensitive than in CD1 mice to inhibition by DAMGO. The results suggest probable differences in the specific neural locations of opioid receptor subtypes in certain inbred strains of mice with varying sensitivities to the behavioral effects of morphine.

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