DSP4-induced noradrenergic lesions increase beta-adrenergic receptors and hippocampal electrophysiological responsiveness.
Following profound (greater than 90%) depletions of norepinephrine (NE) by the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), the numbers of beta-adrenergic receptors were significantly increased (20-25%) in rat hippocampal and somatosensory cortical membranes; however, the numbers of alpha 1-adrenergic receptors and the affinities of both types of receptors were unaffected. This selective up-regulation of beta-adrenergic receptors was evident 1 week after DSP4 administration and was maintained for at least 2 more weeks. In electrophysiological experiments in the hippocampal slice preparation, responses to threshold as well as maximal concentrations of isoproterenol were enhanced 150% and 33%, respectively, in the DSP4-lesioned animals. The results demonstrate that nearly complete depletion of brain NE produced by administration of DSP4, like that produced by 6-hydroxydopamine, results in increased numbers of beta- but not alpha-adrenergic receptors, and suggest that the density of the former are regulated by afferent noradrenergic fibers. Furthermore, the functional significance of the increased number of hippocampal beta-adrenergic receptors is directly manifested in a greater electrophysiological responsiveness to an exogenously administered beta-adrenergic receptor agonist.
D000200:Action Potentials / Q000187:drug effects; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D009638:Norepinephrine / Q000502:physiology*; D010869:Pindolol / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013997:Time Factors
D000588:Amines; D001596:Benzylamines; D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D007545:Isoproterenol; C012102:DSP 4; D009638:Norepinephrine