Stringfield, S. J. | Search bioRxiv

bioRxiv2023

Changes in dorsomedial striatum activity mediate expression of goal-directed vs. habit-like cue-induced cocaine seeking

A preclinical model of cue exposure therapy, cue extinction, reduces cue-induced cocaine seeking when drug seeking is goal-directed but not habitual. Goal-directed and habitual behaviors differentially rely on the dorsomedial striatum (DMS) and dorsolateral striatum (DLS), but the effects of cue extinction on dorsal striatal responses to cue-induced drug seeking are unknown. We used fiber photometry to examine how dorsal striatal intracellular calcium and extracellular dopamine activity differs between goal-directed and habitual cue-induced cocaine seeking and how it is impacted by cue extinction. Rats trained to self-administer cocaine paired with an audiovisual cue on schedules of reinforcement that promote goal-directed or habitual cocaine seeking had different patterns of dorsal striatal calcium and dopamine responses to cue-reinforced lever presses. Cue extinction reduced calcium and dopamine responses during subsequent drug seeking in the DMS, but not in the DLS. Therefore, cue extinction may reduce goal-directed behavior through its effects on the DMS, whereas habitual behavior and the DLS are unaffected.

neuroscience↗

bioRxiv2022

Nicotine enhances intravenous self-administration of cannabinoids in adult rats

IntroductionNicotine and cannabis are commonly used together, yet few studies have investigated the effects of concurrent administration of both drugs. Nicotine exhibits reinforcement enhancing effects by promoting the reinforcing properties of stimuli including other drugs. As many studies of this effect have used non-contingent nicotine, we implemented a dual-self-administration model where rats are given simultaneous access to two drugs and choose which to self-administer throughout a session. Here, we investigated the effect of self-administered or non-contingently delivered nicotine on cannabinoid self-administration. MethodsAdult male rats were allowed to self-administer the synthetic cannabinoid WIN 55,212-2 (WIN) intravenously, with or without subcutaneous nicotine injections before each session. A separate group of animals were allowed to self-administer WIN, nicotine, or saline using a dual-catheter procedure, where each solution was infused independently and associated with a separate operant response. A third group of male and female rats were allowed to self-administer delta-9-tetrahydrocannabinol (THC) with or without pre-session injections of nicotine. ResultsNicotine injections increased self-administration of WIN and THC. During dual self-administration, nicotine availability increased saline and WIN infusions but nicotine intake was not changed by WIN or saline availability. Rats preferred nicotine over saline, but preferred nicotine and WIN equally when both were available. The effect of nicotine on cannabinoid self-administration was acute and reversible when nicotine was no longer present. ConclusionsThese results expand our understanding of the ability of nicotine to enhance reinforcement of other drugs of abuse and suggest that co-use of nicotine and cannabinoids promotes cannabinoid use in excess of what would be taken alone. ImplicationsThis study utilizes a dual intravenous self-administration model to investigate the ability of nicotine to enhance cannabinoid intake. Our results demonstrate that the reinforcement enhancing properties of nicotine on drug use extend to include cannabinoids, but that this effect occurs specifically when nicotine is administered alongside the cannabinoid. Interestingly, cannabinoid use did not promote nicotine intake, suggesting this mechanism of reinforcement is specific to nicotine.

neuroscience↗