Functional supersensitivity to adrenergic agonists in the rat after DSP-4, a selective noradrenergic neurotoxin.
Rats treated with DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], a selective noradrenergic neurotoxin, showed no differences compared to control rats in the number of head dips, a measure of exploratory behavior. Since a previous neurochemical investigation had demonstrated that DSP-4 rats have supersensitive alpha 2- and beta-adrenergic receptors in certain regions of the central nervous system, the behavior of these animals was also examined after the injection of clonidine, an alpha 2 agonist, and clenbuterol, a beta agonist. These drugs reduced, in a dose-dependent manner, the head-dipping of both control and DSP-4 rats. However, this effect was of greater magnitude in DSP-4 animals. Control experiments suggested that the response to clonidine and clenbuterol was mediated centrally by alpha 2 and beta receptors, respectively. Other behavioral experiments with agonists of the dopaminergic and serotoninergic systems indicated that these neurotransmitter systems were unchanged in DSP-4 animals. The results are discussed in terms of the selective action of DSP-4 and the responsiveness of DSP-4 rats to adrenergic agonists. The DSP-4-treated rat may constitute a new model of functional supersensitivity to adrenergic agonists.
D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001596:Benzylamines / Q000494:pharmacology*; D002976:Clenbuterol / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology*; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D013566:Sympathomimetics / Q000494:pharmacology*
D000588:Amines; D001596:Benzylamines; D009498:Neurotoxins; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D013566:Sympathomimetics; D003000:Clonidine; C012102:DSP 4; D009638:Norepinephrine; D002976:Clenbuterol