Enhanced Sensory-Cognitive Processing by Activation of Nicotinic Acetylcholine Receptors.

Activation of nicotinic acetylcholine receptors (nAChRs) enhances sensory-cognitive function in human subjects and animal models, yet the neural mechanisms are not fully understood. This review summarizes recent studies on nicotinic regulation of neural processing in the cerebral cortex that point to potential mechanisms underlying enhanced cognitive function. Studies from our laboratory focus on nicotinic regulation of auditory cortex and implications for auditory-cognitive processing, but relevant emerging insights from multiple brain regions are discussed. Although the major contributions of the predominant nAChRs containing α7 (homomeric receptors) or α4 and ß2 (heteromeric) subunits are well recognized, recent results point to additional, potentially critical contributions from α2 subunits that are relatively sparse in cortex. Ongoing studies aim to elucidate the specific contributions to cognitive and cortical function of diverse nAChRs. IMPLICATIONS: This review highlights the therapeutic potential of activating nAChRs in the cerebral cortex to enhance cognitive function. Future work also must determine the contributions of relatively rare but important nAChR subtypes, potentially to develop more selective treatments for cognitive deficits.

Nicotine exposure beginning in adolescence enhances the acquisition of methamphetamine self-administration, but not methamphetamine-primed reinstatement in male rats.

BACKGROUND: Nicotine is commonly abused in adolescence and is believed to be a "gateway" to other drugs of abuse [e.g., methamphetamine (METH)]. The relationship between early nicotine exposure and later METH use is complicated because the majority of juvenile smokers continue to use cigarettes into adulthood. Thus, the present investigation examined the individual and combined contribution of adolescent and adult nicotine exposure on METH self-administration. METHODS: Forty-three male rats were pretreated with saline or nicotine (0.16 or 0.64 mg/kg, SC) from postnatal day (PD) 35-50. On PD 51, subjects were split into the following groups: SAL-SAL, 0.16-0.16, 0.16-SAL, 0.64-0.64, and 0.64-SAL. Rats were then trained to lever press for METH (0.05 mg/kg) for seven days on an FR1 and seven days on an FR3 reinforcement schedule. After acquisition training, rats underwent 14 days of extinction and were then tested for METH-induced primed reinstatement (1.0mg/kg, IP). RESULTS: Data showed that rats receiving continuous injections of the low dose of nicotine (0.16-0.16) obtained more METH infusions versus the control group (SAL-SAL) on an FR1 and FR3 schedule. In addition, rats on the FR3 schedule that received a low dose of nicotine during the adolescent period only (0.16-SAL) had more METH intake than the control group (SAL-SAL). Interestingly, the high dose of nicotine exposure had no effect on METH intake and neither nicotine dose altered METH seeking behavior. CONCLUSIONS: Low dose exposure to nicotine during adolescence enhances the reinforcing effects of METH, while heavier exposure has no effect on METH intake.