DSP-4-induced depletion of brain norepinephrine produces opposite effects on exploratory behavior 3 and 14 days after treatment.
Exploratory behavior of a complex novel environment was examined 3 and 14 days following treatment with the noradrenergic-selective neurotoxin, DSP-4. This toxin significantly decreased norepinephrine concentrations in neocortex and hippocampus but not hypothalamus. DSP-4 significantly increased exploratory behavior in animals tested 3 days after treatment. In contrast, exploratory behavior was decreased in animals tested 14 days after treatment. The effect of DSP-4 at 3 days is similar to treatments that act to inhibit noradrenergic function such as administration of the alpha 1-antagonist, prazosin, or the alpha 2-agonist, clonidine. The effect of DSP-4 at 14 days resembles that observed following treatment with the alpha 1-agonist, phenylephrine, or the alpha 2-antagonist, idazoxan. These data provide additional support for a role of noradrenergic systems in exploratory behavior. The simplest explanation for the time dependent effects of DSP-4 on exploratory behavior is the occurrence of the slow development of a supersensitivity of cerebral systems affected by norepinephrine.
Berridge
C W
CW
Department of Neuroscience, University of Florida College of Medicine, Gainesville 32610.
Dunn
A J
AJ
D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D019329:Idazoxan; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D012149:Restraint, Physical; D013566:Sympathomimetics / Q000494:pharmacology*
D001596:Benzylamines; D004146:Dioxanes; D013566:Sympathomimetics; D010656:Phenylephrine; D008734:Methoxyhydroxyphenylglycol; D003000:Clonidine; C012102:DSP 4; D009638:Norepinephrine; D011224:Prazosin; D019329:Idazoxan