Depression and stress are two states during cocaine abstinence which users identify as precipitating relapse, and JDTic may have properties which attenuate both.

β2 subunit containing nicotinic acetylcholine receptors (β2*nAChRs; *denotes assembly with other subunits) are critical for nicotine self administration and nicotine-associated dopamine (DA) release that supports nicotine reinforcement. The α6 subunit assembles with β2 on DA neurons where α6β2*nAChRs regulate nicotine-stimulated DA release at neuron terminals. Using local infusion of alpha-conotoxin MII (α-CTX MII), an antagonist with selectivity for α6β2*nAChRs, the purpose of these experiments was to determine if α6β2*nAChRs in the nucleus accumbens (NAc) shell are required for motivation to self-administer nicotine. Long Evans rats lever pressed for 0.03 mg/kg i.v. nicotine accompanied by light+tone cues (NIC) or for light+tone cues unaccompanied by nicotine (CUEonly). Following extensive training, animals were tested under a progressive ratio (PR) schedule that required an increasing number of lever presses for each nicotine infusion and/or cue delivery. Immediately prior to each PR session, rats received micro-infusions of α-CTX MII (0, 1, 5, or 10 pmols/side) into the NAc shell or the overlying anterior cingulate cortex. α-CTX MII dose-dependently decreased break points and number of infusions earned by NIC rats following infusion into the NAc shell but not the anterior cingulate cortex. Concentrations of α-CTX MII that were capable of attenuating nicotine self administration did not disrupt locomotor activity. There was no effect of infusion on lever pressing in CUEonly animals and NAc infusion α-CTX MII did not affect locomotor activity in an open field. These data suggest that α6β2*nAChRs in the NAc shell regulate motivational aspects of nicotine reinforcement but not nicotine-associated locomotor activation.

Highlights d Exposure to the psychedelic drug DOI results in enduring molecular adaptations d Post-acute DOI unveils phenotypes akin to antidepressant adaptations d Concurrent occurrence of synaptic plasticity mediated via 5-HT

No abstract