Sensitized Increase of Period Gene Expression in the Mouse Caudate/Putamen Caused by Repeated Injection of Methamphetamine

Abstract

Methamphetamine (MAP) causes the sensitization phenomena not only in MAP-induced locomotor activity, dopamine release, and Fos expression, but also in MAP-induced circadian rhythm. Cocaine-induced sensitization is reportedly impaired in Drosophila melanogaster mutant for the Period (Per) gene. Thus, sensitization may be related to induction of the Per gene. A rapid induction of mPer1 and/or mPer2 in the suprachiasmatic nucleus after light exposure is believed to be necessary for light-induced behavioral phase shifting. Although the caudate/putamen (CPu) expresses mPer1 and/or mPer2 mRNA, the function of these genes in this nucleus has not yet been elucidated. Therefore, we examined whether MAP affects the expression of mPer1 and/or mPer2 mRNA in the mouse CPu. Injection of MAP augmented the expression of mPer1 but not mPer2 or mPer3 in the CPu, and this MAP-induced increase in mPer1 expression lasted for 2 h. Also, the MAP-induced increase of mPer1 mRNA was strongly antagonized by pretreatment with a dopamine D1 receptor and N-methyl-D-aspartate (NMDA) receptor antagonist, but not by a D2 receptor antagonist. Interestingly, application of either the D1 or the D2 agonist alone did not cause mPer1 expression. The present results demonstrate that activation of both NMDA and D1 receptors is necessary to produce MAP-induced mPer1 expression in the CPu. Repeated injection of MAP caused a sensitization in not only the locomotor activity but also mPer1 expression in the CPu without affecting the level of mPer2, mPer3, or mTim mRNA. Thus, these results suggest that MAP-induced mPer1 gene expression may be related to the mechanism for MAP-induced sensitization in the mouse.

Ethological analyses of crayfish behavior: a new invertebrate system for measuring the rewarding properties of psychostimulants

“…For instance, the trace amine tyramine (TA) appears to play an integral role in the development of behavioral sensitization to cocaine [38] such that circadian gene regulation, TA biosynthesis and behavioral sensitization are tightly coupled in fruit flies [2]. Interestingly, subsequent work in mammals demonstrated the importance of circadian rhythmicity for psychostimulant sensitization [1,44] and, furthermore, identified a population of high-affinity TA receptors in the ventral tegmental area [11], a focal region of DA-rich cell bodies thought to be a primary component of reward circuitry in the mammalian brain. Although trace amines like TA have historically received less experimental attention than other monoamines, there exists a large literature documenting their relationship to disturbances in affect and cognition (see ref.…”

The role of mPer1 in morphine dependence in mice

“…The Period (Per) encodes one of the essential elements involved in the transcription/translation-based auto-regular loop of the endogenous master clock (Reppert and Weaver, 2001). Three homologues of Drosophila Per genes were subsequently identified in mice (mPer1, mPer2, and mPer3) (Albrecht, 2002), leading to great progress in elucidation of the molecular mechanism underlying circadian rhythm in the CNS.It has been shown that repeated administration of methamphetamine caused behavioral sensitization as well as sensitized expression of mPer1 (Nikaido et al, 2001). Some studies implicate a role for Per genes in drug-induced behavioral sensitization processes.…”

“…It has been shown that repeated administration of methamphetamine caused behavioral sensitization as well as sensitized expression of mPer1 (Nikaido et al, 2001). Some studies implicate a role for Per genes in drug-induced behavioral sensitization processes.…”

Effects of Methamphetamine on Circadian Rhythms of Mice

“…A single injection of MAP was shown to induce Period1 gene expression in the Piriform cortex (PC) and Caudate-Putamen (CPU) in the mouse brain, but not the SCN (Nikaido, Akiyama et al 2001). In addition, chronic MAP shifts the phase of circadian expression of Period1, Period2 and Bmal1 mRNA in CPU and Parietal cortex (PtA) and induces Clock mRNA expression in CPU of rats (Masubuchi, Honma et al 2000).…”

“…Administration of a high dose of MAP to intact C57BL/6 mice produces two it induces the expression of these genes in areas such as Caudate-Putamen (CPU) in mice (Nikaido, Akiyama et al 2001). Similarly, chronic MAP does not affect the Per1 expression profile in the SCN of rats ex vivo (Masubuchi, Honma et al 2000) or the firing activity of SCN neurons in vitro (Moriya, Fukushima et al 1996).…”