Performance of alpha7 nicotinic receptor null mutants is impaired in appetitive learning measured in a signaled nose poke task.

Wild-type and mutant mice lacking expression of alpha5, alpha7, beta2, beta3, or beta4 neuronal nicotinic cholinergic receptors (nAChRs) were compared on a signaled nose poke task, a multi-phased task used to measure appetitive learning and impulsivity. In the early phases of training, mutants of all nicotinic lines did not differ compared to wild types in the days to reach criterion when mice were required to nose poke for a sucrose reward on FR1 or FR3 schedules, or in their ability to respond to an auditory clicker to receive a sucrose reward. However, mutants lacking alpha7 nAChRs, but not lines lacking other nAChRs, showed impairments when task difficulty was increased such that an auditory stimulus was presented on a variable schedule and mice were required to withhold their responses until the presentation of the auditory cue to obtain a reward. alpha7 mutants were impaired compared to wild types in appetitive learning as measured by the percentage of conditioned responses but overcame their deficits with extensive training for 10 days. However, when efficiency ratios were used to measure impulsivity, alpha7 mutants exhibited lower efficiency ratios even after 10 days of training. These results support a role of the alpha7 nicotinic receptor in mediating appetitive learning and suggest a potential role for the alpha7 nAChRs in the regulation of behavioral disinhibition.

Deletion of the alpha7 nicotinic receptor subunit gene results in increased sensitivity to several behavioral effects produced by alcohol.

BACKGROUND: The finding that most people with alcoholism are also heavy smokers prompted several research groups to evaluate the effects of ethanol on neuronal nicotinic acetylcholine receptor (nAChR) function. Data collected in vitro indicate that physiologically relevant concentrations of ethanol inhibit the functional activation of homomeric alpha7 nAChRs, which are one of the most abundant nAChR subtypes expressed in the mammalian brain. The studies outlined here used alpha7 gene knockout (null mutant) mice to evaluate the potential role of alpha7 nAChRs in modulating selected behavioral and physiological effects produced by ethanol. METHODS: Current evidence indicates that many responses to ethanol are not genetically correlated. Therefore, the authors measured the effects of acute administration of ethanol on several behaviors that are altered by both ethanol and nicotine: two tests of locomotor activity, acoustic startle, prepulse inhibition of acoustic startle, and body temperature. Ethanol-induced durations of loss of righting reflex and ethanol elimination rates were also determined. These studies used null mutant (alpha7(-/-)) and wild-type (alpha7(-/-)) mice. RESULTS: Relative to alpha7(+/+) mice, alpha7(-/-) mice were more sensitive to the activating effects of ethanol on open-field activity, ethanol-induced hypothermia, and duration of loss of the righting response. Deletion of the alpha7 gene did not influence the effects of ethanol on Y-maze crossing or rearing activities, acoustic startle, or prepulse inhibition of startle. Gene deletion did not alter ethanol metabolism. CONCLUSIONS: These results indicate that some but not all of the behavioral effects of ethanol are mediated in part by effects on nAChRs that include the alpha7 subunit and may help to explain the robust association between alcohol consumption and the use of tobacco.