Role of CNS alpha1-adrenoceptor activity in central fos responses to novelty.

The present study investigated, by use of fos immunohistochemistry, whether the functional activity of alpha(1)-adrenoceptors is elevated during heightened behavioral activity in brain regions shown earlier to contain motoric alpha(1)-receptors. In confirmation, marked c-fos responses that were blocked by an alpha(1)-antagonist (prazosin) were found in four of these brain regions (secondary motor, cingulate, piriform cortices, and nucleus accumbens) of animals exposed to a mildly novel environment (clean cage), which elicits a high degree of sustained exploratory activity. Experimental restriction of exploratory activity in the novel cage by a small enclosure did not reduce the fos responses in these areas, and in fact, enhanced gene expression when carried out in home-caged animals suggesting that the fos response may be more closely associated with the motivation to be active rather than activity itself. Experiments with locally administered alpha(1)-agonists and antagonists in the cortex by reverse dialysis showed that the above mentioned alpha(1)-dependent-fos responses were the result of activation of local alpha(1)-receptors in these brain regions. Unlike the aforementioned brain regions, the fos response of the locus coeruleus was not blocked by prazosin, and this nucleus also showed a marked fos increase to prazosin itself possibly as a compensatory response to the blockade of forebrain alpha(1)-receptors.