Environmental novelty modulates the induction and expression of single injection-induced behavioral sensitization to morphine

Abstract

Opioid addiction is a growing public health problem, being currently considered an epidemic in the United States. Investigating the behavioral effects of opioids and the factors influencing their development becomes of major importance. In animals, the effects of drugs of abuse can be assessed using the behavioral sensitization model, which shares similar neuronal substrates with drug craving in humans. Importantly, novelty plays a critical role on the development of behavioral sensitization. The aim of the present study was to investigate the influence of a new environment on both the induction and expression phases of morphine (Mor)-induced behavioral sensitization in the two-injection protocol. Mice were initially treated with saline, 15 or 30 mg/kg Mor (induction phase), and subsequently challenged 7 days later with 15 mg/Kg Mor (expression phase). Locomotor frequency was evaluated during behavioral sessions, performed as follow: induction session on a novel environment and expression on a familiar open-filed apparatus; induction session on animals' home-cage (familiar environment) and expression session on an unknown open-filed apparatus; both sessions on novel environments; and both sessions on familiar contexts. Mor-induced behavioral sensitization was only observed when animals were exclusively exposed to novelty during the induction phase, not being observed when both the induction and expression sessions were performed on similar (novel or familiar) environments. Our results suggest that the development of behavioral sensitization to Mor depends on the exposure to novelty during the induction phase and absence of novelty during the expression phase, indicating a complex relationship between novelty and Mor-induced behavioral effects.

Context-dependent effects of the CB1 receptor antagonist rimonabant on morphine-induced behavioral sensitization in female mice

“…Of note, the fact that rimonabant also blocked the expression of morphine-induced behavioral sensitization when administered in a novel environment also suggest that dopamine activation is necessary for rimonabant to exert its effects. Studies have shown that acute and chronic responses to drugs of abuse can be modulated by environmental novelty ( Caprioli et al, 2007 ), and exposure to novelty can potentiate the development of rapid-onset morphine-induced behavioral sensitization ( Trombin et al, 2018 ). Importantly, these effects may be mediated by novelty-induced dopamine activation, as exposure to novelty can activate similar neuronal substrates that mediate the rewarding effects of drugs of abuse, particularly dopamine signaling within the mesolimbic system ( Bardo et al, 1996 ).…”

“…injection of 17.8 mg/kg morphine, respectively ( Koek et al, 2012 ). Pretreatment time was also determined based on previous studies from our laboratory showing that a 30 min pretreatment is effective in inducing behavioral sensitization to morphine in mice ( Hollais et al, 2014 ; Marinho et al, 2015 ; Trombin et al, 2018 ). The same pretreatment time used during the sensitization phase (30 min) was used for the morphine challenge.…”

“…The doses of morphine and rimonabant were based on previous studies from our laboratory using similar procedures in mice ( Hollais et al, 2014 ; Marinho et al, 2015 ; Marinho et al, 017 ; Trombin et al, 2018 ). Locomotor sensitization to drugs, including morphine, is a dose-dependent phenomenon ( Powell and Holtzman, 2001 ).…”

Effect of Morphine Administration on Social and Non-Social Play Behaviour in Calves

“…A reduction in lying time indirectly infers that these calves may have been more active at this time than calves given saline. Similarly, morphine administration increased locomotor activity in rats [28], primates [13] and sheep [18]. Verbeek et al [18] hypothesized that this increase in activity was related to increased goal directed or approach behaviour mediated by the dopaminergic pathways stimulated through the administration of morphine.…”

The roles of ubiquitin–proteasome system and regulator of G protein signaling 4 in behavioral sensitization induced by a single morphine exposure

“…Taken together, we hypothesize that RGS protein degradation, possibly mediated by UPS, might be related with opioid addiction. In this study, we aimed to conduct a preliminary investigation of the regulatory roles of RGS4 and UPS in the development of morphine‐induced behavioral sensitization in rats, a well‐recognized animal model of opioid addiction (Liu et al., 2021; Trombin et al., 2018).…”