URB597 abrogates anxiogenic and depressive behaviors in the methamphetamine-withdrawal mice: Role of the cannabinoid receptor type 1, cannabinoid receptor type 2, and transient receptor potential vanilloid 1 channels

Abstract

Background: Methamphetamine is an addictive stimulant that possesses toxicity in the brain when taken repeatedly or at higher doses. Methamphetamine neurotoxicity is associated with numerous forms of mental impairment, including depression and anxiety. Evidence has also demonstrated that the endocannabinoid system is involved in the regulation of anxiety and depression. Aims: This study was designed to determine the involvement of the endocannabinoid system in anxiety- and depression-related behaviors in methamphetamine-withdrawal male NMRI mice. Methods: The elevated plus maze and forced swim test were used to assess the level of anxiety and depression. Results: We found that methamphetamine (30 mg/kg, intraperitoneal) evoked depressive- and anxiogenic-like effects at 3 days post-administration. Injection of URB597 (5–10 ng/mouse, intracerebroventricular), 10 min before the test, prevented the emotional deficits induced by methamphetamine withdrawal. Moreover, the cannabinoid receptor type 1 antagonist AM251 (1 μg/mouse) or cannabinoid receptor type 2 antagonist AM630 (5 and 10 μg/mouse) suppressed the antidepressant activity in the methamphetamine-withdrawal mice treated with URB597. The transient receptor potential vanilloid 1 antagonist capsazepine (25 μg/mouse) prevented while capsazepine (100 μg/mouse) potentiated the antidepressant efficacy in the methamphetamine-withdrawal mice treated with URB597. The higher dose of AM630 and two higher doses of capsazepine had antidepressant efficacy, by themselves. Furthermore, capsazepine (50 μg/mouse) increased locomotion in the methamphetamine-withdrawal mice treated with URB597. Conclusions: The results suggest that URB597 has a potential for preventing methamphetamine withdrawal-evoked anxiety and depression. Cannabinoid type 1 receptors, cannabinoid type 2 receptors and transient receptor potential vanilloid 1 differently affect depression-related behaviors in methamphetamine-withdrawal mice treated with URB597.

Footshock-Induced Abstinence from Compulsive Methamphetamine Self-administration in Rat Model Is Accompanied by Increased Hippocampal Expression of Cannabinoid Receptors (CB1 and CB2)

“…In contrast to our findings, URB597, an inhibitor of FAAH, was reported to suppress METH-seeking behavior in mice [ 63 ]. The dichotomous findings may be related to species differences since FAAH inhibition was found to increase nicotine [ 64 ] and alcohol reward [ 65 ] in mice, but reduced nicotine [ 66 ] or alcohol [ 67 ] reward in rats.…”

More than just smoke: Psychopharmacology of cannabinoids

“…Calpe-López et al (2021) reported that CBD prevents priming- and stress-induced reinstatement of the conditioned place preference induced by cocaine in mice, suggesting that CBD could reduce cocaine seeking after a period of abstinence. Finally, Ebrahimi-Ghiri et al (2021) examined whether the fatty-acid amide hydrolase (FAAH) inhibitor, URB597, could abrogate anxiogenic and depressive behaviors in the methamphetamine-withdrawal mouse model. Results suggest that URB597 has a potential to prevent methamphetamine-withdrawal evoked anxiety and depression.…”

Modulation of Endocannabinoid System Components in Depression: Pre-Clinical and Clinical Evidence

“…Intracerebral injections of AM251 showed similar effects; AM251 (0.8 μg) microinjection to the NAc inhibited antidepressant-like effects induced by the antidepressant phenylglycine derivative (RS)-2-chloro-5-hydroxyphenylglycine in mice that underwent the chronic social defeat stress [ 90 ]; intracerebroventricular (i.c.v.) injection of AM251 (1 μg) prevented anti-depressant effects induced by URB597 [ 76 ]. AM251 (0.28 ng) microinjection to the PFC augmented depressive-like behaviors induced by CUMS [ 77 ] and prevented the therapeutic-like effect of URB597, which decreased immobility time in the FST [ 91 ].…”

“…I.c.v. injection of URB597 (5 and 10 ng) prevented depressive behaviors that were induced by methamphetamine in mice [ 76 ]. Despair-like behavior also was decreased in mice by i.c.v.…”