Anxiolytic-like effects of alpha-2-adrenoceptor agonists on conflict behavior in the rat: pre- versus postsynaptic receptor mechanisms.
The effects of acute pretest administration and chronic posttest administration of clonidine or the selective alpha 2-adrenoceptor agonist UK-14,304 on conflict behavior were investigated. In daily 10-min sessions, water-deprived rats were trained to drink water from a tube that was occasionally electrified (0.25 mA); electrification was signaled by a tone. Prior to treatment, subjects accepted 25-30 shocks/session (punished responding) and consumed approximately 12-15 ml/session (unpunished responding). Acute pretest administration of clonidine or UK-14,304 did not increase punished responding. In contrast, chronic posttest clonidine administration (40 micrograms/kg, IP, twice daily for 8 weeks) resulted in a robust and time-dependent increase in punished responding (60-70 shocks/session) relative to saline-treated controls. Moreover, the selective alpha 2-adrenoceptor agonist UK-14,304 also increased punished responding when administered chronically (1.0 mg/kg, BID). Administration of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine HCl (DSP4, 65 mg/kg, IP) significantly decreased punished responding in control conditioned suppression of drinking sessions. The anticonflict effect associated with chronic posttest clonidine treatment was not altered by DSP4 pretreatment. These findings suggest that chronic posttest alpha 2-adrenoceptor agonist treatment produces an anticonflict effect independent of its actions at presynaptic alpha 2-adrenoceptors.
Department of Pharmaceutical Sciences, College of Pharmacy & AHP, Wayne State University, Detroit, MI 48202.
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D000068438:Brimonidine Tartrate; D003220:Conflict, Psychological; D005260:Female; D009184:Mydriatics / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013566:Sympathomimetics / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D014151:Anti-Anxiety Agents; D001596:Benzylamines; D009184:Mydriatics; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D013566:Sympathomimetics; D015016:Yohimbine; D000068438:Brimonidine Tartrate; C012102:DSP 4