Fentanyl exposure alters rat CB1 receptor expression in the insula, nucleus accumbens and substantia nigra.

Prolonged periods of opioid use have been shown to cause neuroadaptations in the brain's reward circuitry, contributing to addictive behaviors and drug dependence. Recently, considerable focus has been placed on the role of the endocannabinoid system (ECS) and its CB receptors in opioid-driven behaviors. However, opioid-induced neuroadaptations to the ECS remain understudied.

Presynaptic and Postsynaptic Mesolimbic Dopamine D Receptors Play Distinct Roles in Cocaine Versus Opioid Reward in Mice.

Background: Past research has illuminated pivotal roles of dopamine D receptors (DR) in the rewarding effects of cocaine and opioids. However, the cellular and neural circuit mechanisms that underlie these actions remain unclear.

Methods: We employed Cre-LoxP techniques to selectively delete DR from presynaptic dopamine neurons or postsynaptic dopamine D receptor (DR)-expressing neurons in male and female mice.

β-caryophyllene inhibits heroin self-administration, but does not alter opioid-induced antinociception in rodents.

A growing body of research indicates that β-caryophyllene (BCP), a constituent present in a large number of plants, possesses significant therapeutic properties against CNS disorders, including alcohol and psychostimulant use disorders. However, it is unknown whether BCP has similar therapeutic potential for opioid use disorders. In this study, we found that systemic administration of BCP dose-dependently reduced heroin self-administration in rats under an FR2 schedule of reinforcement and partially blocked heroin-enhanced brain stimulation reward in DAT-cre mice, maintained by optical stimulation of midbrain dopamine neurons at high frequencies.