Escalation of methamphetamine self-administration in rats: a dose-effect function

Abstract

Rationale: The transition from stable to escalated drug intake has been demonstrated in rats self-administrating cocaine and heroin using a single dose of drug.

Objectives: To investigate the prolonged exposure to methamphetamine self-administration and the effect of various training doses of methamphetamine on the changes of methamphetamine intake over a 21-day period.

Methods: Two groups of rats were trained in 1-h daily sessions of methamphetamine self-administration [0.033 mg/infusion (inf); approximately 0.066 mg/kg/inf]. Methamphetamine access was increased to 6 h in one group [Long Access (LgA)] or maintained at 1 h in another [Short Access (ShA)]. The same procedure was repeated in rats exposed to different training doses of methamphetamine (0.05, 0.1, and 0.2 mg/kg/inf).

Results: In LgA rats, total and first hour intake of methamphetamine significantly increased compared to ShA rats at various methamphetamine doses. LgA animals, at all doses in the second study, escalated intake to 8-9 mg/kg per 6-h session, with the most rapid escalation occurring at 3-5 days at a methamphetamine dose of 0.1 mg/kg/inf.

Conclusions: The escalation of drug intake observed with extended access is produced at multiple doses of methamphetamine. The rapidity of escalation depends on the dose. Ultimately, all doses in the dose-response study engendered self-administration of the same amount of total drug in a 6-h session in the extended-access group. Results suggest that the rapidity of escalation is dependent on dose and has an upper limit of intake over a period of 21 days.