Program

PO1-1-78

Involvement of cannabinoid CB1 receptors on impairment of prepulse inhibition during withdrawal state after the repeated administration of methamphetamine in mice

[Speaker] Ryo Fukumori:1
[Co-author] Taku Yamaguchi:1, Tsuneyuki Yamamoto:1
1:Pharmacology, Nagasaki International University, Japan

Objective: Endocannabinoid systems play important roles in physiological functions in the central nervous system, such as pain perception, appetite, psychomotor behavior, emotion, reward system and cognitive function. We previously reported that the involvement of cannabinoid CB1 receptors in the reinstatement of methamphetamine-seeking behaviors in rats. On the other hand, repeated administration of methamphetamine causes behavioral sensitization in rodents and human. However, the effects of withdrawal after the repeated administration of methamphetamine on the sensorimotor gating function have been still unclear. In this study, we investigated involvement of cannabinoid CB1 receptors on sensorimotor gating function during withdrawal state after the repeated administration of methamphetamine in mice.

Method: We used male ICR-strain mice (genetic control: wild-type) and the cannabinoid CB1 receptor knockout mice. Mice were subcutaneously administered methamphetamine at the dose of 1.8 mg/kg or saline, every other day for 30 days (15 injections). Behavioral sensitization was evaluated by locomotor activity in the open-field test. 10 or 30 days after withdrawal, the mice were tested a sensorimotor gating function by prepulse inhibition test. AM251 (3.2 mg/kg), a cannabinoid CB1 receptor antagonist, was co-administrated with methamphetamine (AM251 co-administered group) or singly administered 30 min before the prepulse inhibition test during withdrawal state after the repeated administration of methamphetamine (AM251 single-administered group).

Result: In wild-type mice, locomotor activity was significantly enhanced by the repeated administration of methamphetamine. Prepulse inhibition of the acoustic startle response was suppressed during withdrawal of repeated methamphetamine, without changes in startle amplitude. On the other hand, in CB1 receptor knockout mice, the locomotor activity was not enhanced by repeated administration of methamphetamine. Furthermore, the prepulse inhibition in CB1 receptor knockout mice were not impaired by repeated administration of methamphetamine. In addition, the prepulse inhibition in AM251 co-administered group was not suppressed by repeated administration of methamphetamine. However, the prepulse inhibition in AM251 single-administered group was significantly impaired by repeated administration of methamphetamine.

Conclusion: These findings suggest that activation of the cannabinoid CB1 receptors could lead to the development of behavioral sensitization and sensorimotor gating deficits during withdrawal state after the repeated administration of methamphetamine.

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