Development of stereotyped behaviors during prolonged escalation of methamphetamine self-administration in rats.

RATIONALE: Experimental animal studies have shown that repeated administration of psychostimulants, such as methamphetamine (METH), results in an altered behavioral response profile, which includes the sensitization of both locomotor and stereotyped behaviors. Although sensitization of these behaviors has been characterized in detail during bolus, investigator-administered drug administration, little is known about the development or expression of stereotypies during psychostimulant self-administration.

OBJECTIVE/METHODS: The present study investigated in rats the expression of focused stereotyped behaviors during an extended access, escalation procedure of METH self-administration. Over several weeks during stepwise-extended daily access to METH (3, 6, and 12 h) followed by exposure to 24-h "binges," rats gradually increased daily drug intake.

RESULTS: During the escalation procedure, the rats' behavioral response evolved from locomotor activation to progressively more focused stereotypies, culminating in continuous oral behaviors (licking, gnawing, and chewing), interrupted only by episodic lever presses. Sensitization of stereotyped behaviors was evident, particularly with regard to oral behaviors that exhibited a more rapid onset and intensification in the apparent absence of greater drug intake.

CONCLUSIONS: Our data demonstrate that stepwise-extended daily access to METH (3, 6, 12, and 24 h) self-administration in rats closely approximates motivational, pharmacokinetic, as well as behavioral patterns of human METH abuse. The accompanied appearance of sensitization of intense focused stereotyped behaviors, which is probably a consequence of escalation of drug intake, resembles stereotypies associated with investigator-initiated METH administration and may parallel the development of stimulant-induced psychosis seen in human abusers.