Impairment of opiate‐mediated behaviors by the selective TRPV1 antagonist SB366791

Abstract

Transient receptor potential vanilloid type 1 (TRPV1), the archetypal member of the vanilloid TRP family, was initially identified as the receptor for capsaicin, the pungent ingredient in hot chili peppers. We previously demonstrated that TRPV1 in the dorsal striatum significantly contributes to morphine reward by using the conditioned place preference paradigm in mice; however, it is unknown whether TRPV1 has the same effect in other reward models. In this study, we investigated the role of TRPV1 in morphine reward by using a self-administration paradigm in rats. We found that treatment with a selective TRPV1 antagonist, SB366791, significantly decreased morphine self-administration on a fixed-ratio 1 schedule or a progressive ratio schedule of reinforcement. In addition, treatment with another selective TRPV1 antagonist, AMG9810, not only significantly prevented morphine self-administration but also prevented morphine-induced c-fos expression in the nucleus accumbens. Furthermore, administration of SB366791 decreased an anxiolytic-like effect during the morphine abstinence period. Moreover, treatment with SB366791 significantly decreased morphine-priming reinstatement. Taken together, our findings suggest that blockade of TRPV1 receptors could provide an approach to limiting morphine addiction.

Impact of acute and chronic nicotine administration on midbrain dopaminergic neuron activity and related behaviours in TRPV1 knock‐out juvenile mice

“…Several recent studies have shown that TRPV1 channels play a crucial role in drug addiction disorders (Ma et al, 2017; Tian et al, 2018) highlighting the need to further explore the role of TRPV1R in the modulation of the reward system. VTA DA neurons, together with their afferents to the NAc and prefrontal cortex, constitute a crucial neuronal circuit in drug addiction and drug‐seeking behaviour (Kauer & Malenka, 2007).…”

“…Unexpectedly, our results show a modulatory role of TRPV1 on the effects of chronic nicotine administration in mice behaviour, though not at the cellular level. This discrepancy may suggest that TRPV1 receptor control on nicotine‐induced locomotor sensitization does not depend on VTA TRPV1R but on TRPV1R expressed in more downstream structures of the mesolimbic dopaminergic system, such as NAc (Ma et al, 2017; You et al, 2019). Future experiments should be conducted to explore this prospect.…”

“…For instance, TRPV1Rs might be important in the control of alcohol preference and consumption (Blednov et al, 2010). Their blockage reduces morphine intravenous self‐administration (Ma et al, 2017) as well as morphine‐induced conditioned place preference (Hong et al, 2017). Another preclinical study suggested that TRPV1R activation is involved in cocaine seeking behaviour (Adamczyk et al, 2012).…”

Side Effects of Opioids Are Ameliorated by Regulating TRPV1 Receptors

“…The same result is found in the NAc; for example, TRPV1 knock-out mice do not exhibit morphine reward responses, and intraperitoneal and intra-NAc injections of SB366791 reduce morphine-induced CPP in wild-type mice [ 56 ]. Furthermore, TRPV1 has a consistent effect in the morphine self-administration paradigm [ 34 ], which may relevantly model drug-taking behavior in a natural environment and be regarded as a gold-standard indicator of addiction [ 59 ]. Blocking the TRPV1 receptor with SB366791 significantly reduces morphine self-administration in rats on a fixed-ratio 1 schedule or a progressive ratio schedule of reinforcement, i.e., suppresses the motivational properties of morphine and its reinstatement or relapse [ 34 ].…”

“…Intrathecal or intraperitoneal pretreatment with the TRPV1 antagonist SB366791 or capsazepine reduces morphine tolerance and the associated thermal hyperalgesia [ 29 ]. In addition, blocking TRPV1 receptors in the reward system, particularly expressed in the striatum and nucleus accumbens (NAc), attenuates opiate-mediated reward behaviors, including conditioned place preference (CPP) and morphine self-administration in rodents [ 34 , 35 ].…”