Growth Hormone Secretagogue Receptor 1A Antagonist JMV2959 Effectively Prevents Morphine Memory Reconsolidation and Relapse


Abstract

Relapse to drug seeking after prolonged abstinence is a major problem in the clinical treatment of drug addiction. The use of pharmacological interventions to disrupt established drug reward memories is a promising strategy for the treatment of drug addiction. A growth hormone secretagogue receptor 1 A antagonist, JMV2959, has been shown to reduce morphine-induced conditioned place preference (CPP) in rats within hours of intervention; thus, JMV2959 is a potential candidate for drug addiction treatment. However, the effect of JMV2959 on reconsolidation to disrupt drug seeking remains unknown. In this study, we assessed the effect of JMV2959 on morphine induced memory reconsolidation to inhibit drug seeking after drug withdrawal. Our results showed that the administration of JMV2959 (6 mg/kg) significantly reduced environmental cue induced CPP, which suggested a preventive effect of JMV2959 on morphine induced memory reconsolidation. Additionally, JMV2959 administration significantly altered the locomotor activity and food and water intake but did not significantly alter the natural reward preference. We concluded that JMV2959 may be an effective candidate to treat drug addiction.

Keywords: JMV2959; addiction; conditioned place preference; ghrelin antagonism; morphine relapse.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The effect of JMV2959 for rats on morphine reconsolidation. (A) Timeline of the Experimental procedure (B) Systematic administration of JMV2959 immediately after exposure to morphine-paired context impaired the reconsolidation of morphine reward memory. The inhibitory effect of JMV2959 on the expression of morphine CPP last for 7d. When given 3?mg/kg morphine priming injection, rats in the group with 6?mg/kg JMV2959 treatment immediately after exposure reinstated the morphine CPP (n = 6-8 per group). *p < 0.01 vs. preconditioning or post-conditioning within group. #p < 0.01 vs. preconditioning or post-treatment within group. (C) Systemic administration of JMV2959 without exposure to morphine reward memory. Pre-C, preconditioning; Post-C, post-conditioning; Post-T1, post-treatment; Post-T14, post-treatment 14; Priming, injected by 3?mg/kg morphine.
FIGURE 2
FIGURE 2
The effect of JMV2959 for rats on locomotor activity. The rats were placed in a photocell cage for 1?h according to the behavioural testing procedure. Then they were injected with vehicle or JMV2959 (0 or 6?mg/kg JMV2959, i.p., respectively) and immediately placed in the chamber. Ambulation behaviour was measured for 60?min. Values are presented as the mean ± SEM (n = 6) *p < 0.05, **p < 0.01.
FIGURE 3
FIGURE 3
Effect of JMV2959 on natural reward preference. The two-bottle sucrose intake test was performed as described in methods. The difference between Saline group (n = 6) and the group with JMV2959 (6?mg/kg, n = 6) were measured by (A) 2% sucrose and (B) tap water intaking up to 3?days. Two-way repeated measures ANOVA was taken. Values are presented as the mean ± SEM (n = 4). *p < 0.05, **p < 0.01.
FIGURE 4
FIGURE 4
Effect of JMV2959 on food intake and body weight. Weight alteration and food intake test were measured as described in methods. The difference between saline group (n = 6) and the group with JMV2959 (6?mg/kg, n = 6) were recorded by (A) food intaking and (B) body weight in 3?days. Two-way repeated measures ANOVA was taken. Values are presented as the mean ± SEM (n = 4).*p < 0.05,**p < 0.01.
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