Nicotinic acetylcholine receptors in rat forebrain that bind ¹⁸F-nifene: relating PET imaging, autoradiography, and behavior.

Abstract

Nicotinic acetylcholine receptors (nAChRs) in the brain are important for cognitive function; however, their specific role in relevant brain regions remains unclear. In this study, we used the novel compound ¹⁸F-nifene to examine the distribution of nAChRs in the rat forebrain, and for individual animals related the results to behavioral performance on an auditory-cognitive task. We first show negligible binding of ¹⁸F-nifene in mice lacking the β2 nAChR subunit, consistent with previous findings that ¹⁸F-nifene binds to α4β2* nAChRs. We then examined the distribution of ¹⁸F-nifene in rat using three methods: in vivo PET, ex vivo PET and autoradiography. Generally, ¹⁸F-nifene labeled forebrain regions known to contain nAChRs, and the three methods produced similar relative binding among regions. Importantly, ¹⁸F-nifene also labeled some white matter (myelinated axon) tracts, most prominently in the temporal subcortical region that contains the auditory thalamocortical pathway. Finally, we related ¹⁸F-nifene binding in several forebrain regions to each animal's performance on an auditory-cued, active avoidance task. The strongest correlations with performance after 14 days training were found for ¹⁸F-nifene binding in the temporal subcortical white matter, subiculum, and medial frontal cortex (correlation coefficients, r > 0.8); there was no correlation with binding in the auditory thalamus or auditory cortex. These findings suggest that individual performance is linked to nicotinic functions in specific brain regions, and further support a role for nAChRs in sensory-cognitive function.