Effect of footshock stress on place conditioning produced by Δ9-tetrahydrocannabinol and the fatty acid amide hydrolase (FAAH) inhibitor, URB597, in Sprague-Dawley rats

Abstract

Unlike the effect of footshock on THC- and URB597-induced anxiolytic effects, footshock does not promote THC or URB597-induced reward in a conditioned place preference paradigm. However, footshock stress reverses the sedative effects of 1 mg/kg THC.

The endocannabinoid system and drug-associated contextual memories

“…Systemic anandamide administration fails to induce CPP or CPA (Scherma et al , 2008a; Méndez-Díaz et al , 2012), possibly reflecting its low bioavailability due to chemical instability and metabolism mediated by FAAH and other enzymes. A similar result was observed after systemic administration of compounds that increases endogenous anandamide levels through inhibition of its reuptake or hydrolysis (Gobbi et al , 2005; Bortolato et al , 2006; Scherma et al, 2008a,b; Gamaleddin et al , 2013; DeVuono et al , 2017). However, when animals were pretreated with a FAAH inhibitor, anandamide induced CPA, which was prevented by CB 1 antagonism (Scherma et al , 2008a).…”

“…Rewarding effects (CPP) tend to occur at low doses (Braida et al , 2004; Le Foll et al , 2006) and depend not only on CB 1 receptor activation, but also on recruitment of endogenous opioid mechanisms (Braida et al , 2004). In contrast, aversion (CPA) is more commonly observed with high THC doses (Sañudo-Peña et al , 1997; Hutcheson et al , 1998; Cheer et al , 2000; Quinn et al , 2008; DeVuono et al , 2017). In addition to the dose, various other parameters may interfere with THC effects.…”

“…In addition to the dose, various other parameters may interfere with THC effects. The aversiveness induced by this drug is reduced in adolescent rats (Quinn et al , 2008) or when a stress stimulus precedes the conditioning phase (DeVuono et al , 2017). Moreover, THC effects on CPP/CPA are dependent on the previous experience of the subject with the drug, because CPP has been attained, even at doses otherwise aversive to naïve subjects, when the animals receive a previous THC administration (Valjent and Maldonado, 2000).…”

“…However, it attenuates acquisition of CPP induced by cocaine (Luján et al , 2018) and morphine (Markos et al , 2018), and facilitates the extinction of cocaine- and amphetamine-induced CPP (Parker et al , 2004). Moreover, CBD prevents drug- and stress-induced reinstatement of CPP to morphine and cocaine (de Carvalho and Takahashi, 2017), as well as reinstatement of CPP precipitated by methamphetamine (DeVuono et al , 2017). Yet, CBD inhibits CPA precipitated by naltrexone (de Carvalho and Takahashi, 2017).…”

Neutral CB1 Receptor Antagonists as Pharmacotherapies for Substance Use Disorders: Rationale, Evidence, and Challenge

“…In rodents, Δ 9 -THC alone is not self-administered [ 49 , 50 ], although the mixture of Δ 9 -THC and cannabidiol was recently reported to be self-administered by rats [ 51 , 52 ]. In conditioned place preference (CPP) test, Δ 9 -THC typically produces conditioned place aversion [ 53 , 54 ], although place preferences have also been reported [ 55 , 56 ]. In electrical intracranial self-stimulation (ICSS) experiments, Δ 9 -THC was initially reported to facilitate electrical ICSS in rats [ 56 , 57 , 58 ], while other studies found suppression of ICSS in rats and mice [ 59 , 60 , 61 , 62 , 63 ].…”