α1d Adrenoceptor signaling is required for stimulus induced locomotor activity

Abstract

α1 Adrenergic receptors mediate a variety of physiological responses and have been well studied in the cardiovascular and peripheral nervous system. However, their role in the central nervous system remains ill defined because of the lack of highly specific ligands to the α1 receptor subtypes. Here, we have employed gene targeting to elucidate the role of α1d receptors in vivo. In addition to disrupting function, the insertion of the lacZ gene into the α1d receptor locus enabled the specific identification of cells expressing the α1d gene. These cells are localized in the cortex, hippocampus, olfactory bulb, dorsal geniculate and ventral posterolateral nuclei of the thalamus. Behaviorally, the α1d^−/− mice show normal locomotor activity during the subjective day, or resting phase of their cycle. However, during subjective night, or active phase, wheel-running activity is significantly reduced in mutant mice. Furthermore, these mice show a reduction in exploratory rearing behavior in a novel cage environment. Lastly, α1d^−/− mice show reduced hyperlocomotion after acute amphetamine administration. Together, these data reveal the functional importance of α1d adrenoceptors in mediating a variety of stimulus-induced changes in locomotor behaviors. While the sensitivity of noradrenergic neurons to environmental stimuli has been well documented, our data demonstrate that at least some of these post-synaptic responses are mediated by α1d adrenergic receptors.