Contribution of drug doses and conditioning periods to psychomotor stimulant sensitization.
BACKGROUND
Repeated intermittent administration of psychostimulant drugs such as amphetamine and cocaine can cause sensitization (reverse tolerance) to the locomotor-stimulating actions in rats. Sensitization to the stimulant effects of these drugs might contribute to the development and maintenance of addictive behaviors (e.g. compulsive drug use).


OBJECTIVE
Studies were designed to systematically examine how testing conditions affect the development and expression of locomotor sensitization to cocaine and amphetamine.


METHODS
Rats were treated once daily with intraperitoneal (i.p.) administration of amphetamine (0.5-2.0 mg/kg) or cocaine (5.0-20 mg/kg) and placed in activity chambers for 30, 60, or 120 min. All amphetamine-preexposed rats were challenged with 0.5 mg/kg amphetamine, and all cocaine-preexposed rats were challenged with 5.0 mg/kg cocaine for 120-minute activity tests 2 weeks after the final injection.


RESULTS
Rats treated repeatedly with 2.0 mg/kg amphetamine and tested for 60 min in activity chambers or 20 mg/kg cocaine and tested for 30 min in activity chambers were most active in response to the drug challenge. These time points coincide with the maximal behavioral effects of each drug, as measured after the first injection. In contrast, rats treated with 2.0 mg/kg amphetamine and tested for 30 min or 20 mg/kg cocaine and tested for 120 min were least active in response to the drug challenge.


CONCLUSIONS
Repeated association of the peak behavioral effects of high doses of amphetamine or cocaine with the drug-paired environment produces maximal expression of sensitized locomotor responses. Certain testing conditions appear to disrupt sensitization to these same doses of the drugs.
Behavioral Genetics Laboratory, Department of Psychiatry,Harvard Medical School, McLean Hospital, Belmont, MA 02478, USA. mtodtenkopf@mclean.harvard.edu
Mark S
MS
Todtenkopf
William A
WA
Carlezon
D000661:Amphetamine / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D003042:Cocaine / Q000493:pharmacokinetics / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000697:Central Nervous System Stimulants; D000661:Amphetamine; D003042:Cocaine