title: Effects of phencyclidine on schedule-controlled responding following neurotoxic lesions of the striatum.
abstract: The effects of phencyclidine on an operant task were evaluated prior to and after neurotoxic lesions of the striatum in rats. Subjects were trained to respond on a fixed-interval 90-second schedule for water presentation. The degree to which phencyclidine disrupted responding was first evaluated (dose range 1.0-4.0 mg/kg). The subjects were then divided into three matched groups and received bilateral intraventricular injections of 6-hydroxydopamine (6-OHDA) (100 microg), kainic acid (0.25 microg), or vehicle delivered stereotaxically. 6-OHDA was used to destroy the presynaptic neurons of the nigro-striatal pathway and kainic acid was employed to destroy the postsynaptic neurons whose cell bodies are located in the striatum. Following recovery, the phencyclidine dose-response curve was repeated in the fixed-interval paradigm. It was observed that 6-OHDA-induced damage resulted in a rightward shift of the dose-response curve indicating tolerance to phencyclidine and caused a significant depletion of striatal dopamine and gamma-aminobutyric acid (GABA). Kainic acid-induced damage resulted in a leftward shift in the dose-response curve indicating sensitivity to the schedule-disruptive effects of phencyclidine and produced a significant GABA depletion. The vehicle-treated rats exhibited no shift in their sensitivity to phencyclidine. These observations indicate that the effects of phencyclidine are mediated, at least in part, by striatal dopaminergic neurons.
authors.affiliation: Department of Psychology, Busch Campus, Rutgers University, New Brunswick, NJ 08903, USA.
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Carlson
authors.forename: George C
authors.initials: GC
authors.lastname: Wagner
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D016627:Oxidopamine / Q000633:toxicity; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012055:Reinforcement Schedule; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine; D010622:Phencyclidine; D007608:Kainic Acid; D004298:Dopamine