Subchronic phencyclidine administration increases mesolimbic dopaminergic system responsivity and augments stress- and psychostimulant-induced hyperlocomotion. 1998

J D Jentsch, and J R Taylor, and R H Roth
Neuropsychopharmacology Research Unit, Yale University School of Medicine, New Haven, Connecticut 208001, USA.

Previous studies have shown that repeated exposures to phencyclidine (PCP) induces prefrontal cortical dopaminergic and cognitive deficits in rats and monkeys, producing a possible model of schizophrenic frontal cortical dysfunction. In the current study, the effects of subchronic PCP exposure on forebrain dopaminergic function and behavior were further explored. Prefrontal cortical dopamine utilization was reduced 3 weeks after subchronic PCP administration, and the cortical dopaminergic deficit was mimicked by repeated dizocilpine exposure. In contrast, stress- and amphetamine-induced hyperlocomotion, behavior believed to be mediated by activation of mesolimbic dopamine transmission, was enhanced after PCP exposures. Furthermore, haloperidol-induced increases in nucleus accumbens dopamine utilization were larger in magnitude in PCP-treated rats relative to control subjects. These data are the first to demonstrate that repeated exposures to PCP causes prefrontal cortical dopaminergic hypoactivity and subcortical dopaminergic hyper-responsivity in rats, perhaps mimicking alterations in dopaminergic transmission that underlie the behavioral pathology of schizophrenia.

UI MeSH Term Description Entries
D008032 Limbic System A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the AMYGDALA; EPITHALAMUS; GYRUS CINGULI; hippocampal formation (see HIPPOCAMPUS); HYPOTHALAMUS; PARAHIPPOCAMPAL GYRUS; SEPTAL NUCLEI; anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). Limbic Systems,System, Limbic,Systems, Limbic
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D010622 Phencyclidine A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust. 1-(1-Phenylcyclohexyl)piperidine,Angel Dust,CL-395,GP-121,Phencyclidine Hydrobromide,Phencyclidine Hydrochloride,Sernyl,Serylan,CL 395,CL395,Dust, Angel,GP 121,GP121
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D003913 Dextroamphetamine The d-form of AMPHETAMINE. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. d-Amphetamine,Curban,Dexamfetamine,Dexamphetamine,Dexedrine,Dextro-Amphetamine Sulfate,DextroStat,Dextroamphetamine Sulfate,Oxydess,d-Amphetamine Sulfate,dextro-Amphetamine,Dextro Amphetamine Sulfate,Sulfate, Dextroamphetamine,d Amphetamine,d Amphetamine Sulfate,dextro Amphetamine
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D006220 Haloperidol A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279) Haldol

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