Maintenance of amphetamine-induced stereotypy and locomotion requires ongoing dopamine receptor activation. 1997

L H Conti, and D S Segal, and R Kuczenski
Psychiatry Department, University of California, San Diego, School of Medicine, La Jolla 92093, USA.

Amphetamine-induced locomotion and stereotypy depend on dopamine (DA), yet, while extracellular DA concentrations peak early, and then begin to decline, intense stereotyped behaviors continue for relatively prolonged periods. These observations suggest that DA may act as a "trigger" for the entire multiphasic behavioral response. To test this hypothesis in rats, haloperidol (HAL) was injected at different times with respect to (AMPH), and automated and videotaped measures of the behavior were recorded. HAL (0.1 mg/kg, i.p.) or saline was administered either 15 min prior to AMPH (4.0 mg/kg, s.c.); 60 min following AMPH (during the phase of intense oral stereotypy); or 140 min after AMPH (during post-stereotypy locomotion). When administered prior to AMPH, HAL prevented the development of stereotypy, and an increase in locomotion was displayed in place of stereotypy. Haloperidol administration during stereotypy interrupted the response, and resulted in an increase in locomotion for the remainder of the stereotypy phase. In neither of these cases did HAL affect post-stereotypy locomotion. However, when injected during the post-stereotypy phase, HAL caused a decrease in the magnitude of the locomotor response, suggesting that both the stereotypy and locomotor components of the response remain sensitive to HAL at times when DA levels have significantly declined. These results do not support the hypothesis that the early increase in extracellular DA produced by AMPH, acts as a "trigger" for a non-dopaminergic receptor mediated expression of the later phases of the AMPH response. Instead, it appears that both stereotypy and post-stereotypy locomotion remain sensitive to DA receptor blockade when extracellular DA levels are below the levels produced by non-stereotypy-inducing doses of AMPH.

UI MeSH Term Description Entries
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D011954 Receptors, Dopamine Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
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
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
D000697 Central Nervous System Stimulants A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here. Analeptic,Analeptic Agent,Analeptic Drug,Analeptics,CNS Stimulant,CNS Stimulants,Central Nervous System Stimulant,Central Stimulant,Analeptic Agents,Analeptic Drugs,Central Stimulants,Agent, Analeptic,Agents, Analeptic,Drug, Analeptic,Drugs, Analeptic,Stimulant, CNS,Stimulant, Central,Stimulants, CNS,Stimulants, Central
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013239 Stereotyped Behavior Relatively invariant mode of behavior elicited or determined by a particular situation; may be verbal, postural, or expressive. Behavior, Stereotyped,Behaviors, Stereotyped,Stereotyped Behaviors
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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