Fear conditioning and latent inhibition in mice lacking the high affinity subclass of nicotinic acetylcholine receptors in the brain.

Nicotine can enhance performance in several tests of cognition but the specific nicotinic receptor subtypes mediating these effects are largely unknown. Knock out mice lacking the beta2 subunit of the nicotinic receptor were evaluated in fear conditioning and latent inhibition tasks to begin to determine which receptor subtypes mediate the cognitive effects of nicotine. Young (2-4 months) knock out and wild type mice did not differ in either contextual or tone-conditioned fear, but aged (9-20 months) knock out males were impaired in freezing to both context and tone compared to aged wild type males. No differences in fear conditioning were observed between aged knock out and wild type females. Latent inhibition of fear to a pre-exposed tone, as measured by behavioral freezing, was also assessed. Both knock out and wild type mice displayed similar levels of latent inhibition, although overall levels of freezing were lower in knock out mice. These results support a previous study showing spatial learning deficits in aged beta2 subunit knock out mice [EMBO J. 18 (1999) 1235] and suggest that performance of other cognitive tasks may not be influenced by absence of beta2 subunit-containing receptors.