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.
Stone
Eric A
EA
Department of Psychiatry, New York University School of Medicine, New York, New York 10016, USA. eric.stone@nyu.edu
Yan
Lin
L
Ahsan
Mohammed R
MR
Lehmann
Michael L
ML
Yeretsian
Joseph
J
Quartermain
David
D
D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002490:Central Nervous System / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis / Q000379:methods; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D019329:Idazoxan / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D016761:Oncogene Proteins v-fos / Q000378:metabolism*; D010656:Phenylephrine / Q000378:metabolism; D011224:Prazosin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D016761:Oncogene Proteins v-fos; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; C041226:Terazosin; C058525:2-methoxyidazoxan; D011224:Prazosin; D019329:Idazoxan