Dopamine D1 Receptors Participate in Cocaine-Induced Place Preference via Regulation of Ryanodine Receptor Expression

Abstract

Abstract. Ryanodine receptors (RyRs) with three different isoforms in the brain play a role to facilitate Ca 2+ release from the intracellular Ca 2+ pool. Although cocaine is a strongly addictive psychostimulant that dramatically affects the central nervous system function, the role of RyRs and regulation of their expression by cocaine-induced place preference have not yet been defined well. The present study investigated the regulation of RyR expression in mice under intermittent cocaine treatment using the place preference procedure. The cocaine-induced place preference was inhibited by intracerebroventricular pretreatment with dantrolene, a RyRs antagonist, in a dosedependent manner. The levels of RyR-1 and -2 in the limbic forebrain and frontal cortex significantly increased in the cocaine-conditioned mice, whereas that of RyR-3 in these two brain regions showed no changes. Although the up-regulation of RyRs was not affected by blockade of L-type voltage-gated calcium channels, the increase of RyR-1 and -2 in the limbic forebrain and frontal cortex was completely abolished by SCH23390, a selective antagonist of dopamine D 1 receptors, but not by sulpiride, a selective antagonist of dopamine D 2 receptors. These findings indicate that RyRs play a critical role in the development of cocaine-induced place preference and that the upregulation of RyRs in the brain of a mouse showing cocaine-induced place preference is regulated by dopamine D 1 receptors.

Regulatory Mechanisms and Pathophysiological Significance of IP3 Receptors and Ryanodine Receptors in Drug Dependence

“…On the other hand, drugs such as methamphetamine, cocaine, nicotine, and ethanol induced expression of RyRs. Furthermore, the rewarding effect of these drugs was completely suppressed by the RyR antagonist dantrolene (31,32). Our recent reports show that RyR-1 and RyR-2 expressions increase via the PKA signaling pathway coupled to dopamine D 1 -like receptors, although dopamine D 2 -like receptors are not involved in the events (35,36).…”

“…This abused drug-induced rewarding effect was significantly suppressed by dantrolene, a RyR antagonist (31,32). It is therefore considered that RyRs are likely to be also one of the important players in development of the rewarding effect induced by an abused drug via upregulation of intracellular Ca 2+ dynamics as IP 3 R-1.…”

Increase of Type 2 Ryanodine Receptors in Mouse Nucleus Accumbens in the Development and Expression of Morphine-Induced Place Preference

“…These data indicate that morphineconditioning increases the expression of RyR2 in the nucleus accumbens. Our previous study has reported that dopamine D1 receptors show the regulatory potential on RyR2 expression in the develop ment of methamphetamine and cocaineinduced place preference (9,10), which suggests that RyR2 protein expression in the nucleus accumbens observed in the morphineconditioning may be mediated via dopamine D1receptor activation.…”

“…A recent investigation reported that intracerebroventiricular injection of dantrolene, a RyR antagonist, blocked the development of methamphetamine and cocaineinduced place prefer ence (9,10), while there are little available data on the effect of dantrolene on morphineinduced place prefer ence in mice. The present study, therefore examined the role of RyRs in the development and expression of morphineinduced place preference using a conditioned place preference paradigm.…”

“…The conditioning place preference schedule consisted of three phases (preconditioning test, conditioning, and postconditioning test) (10). A) The preconditioning test was performed as follows: mice were placed on the border of both compartments and then the time spent in each compartment during the 900s session was recorded automatically using an infrared beam sensor (BSCPPMS; BrainSienceldea, Co., Ltd., Osaka).…”