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

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Abstract

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.

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Acknowledgments

This research was supported by the National Institutes of Health grant DA01568-30 from the National Institute on Drug Abuse to RK. The authors would like to thank Tina Chan and Kaitlyn Mai for their excellent technical assistance.

Disclosures

M.H., S.M., and R.K. declare no conflicts of interest. A.M. declares that she has received contract research support from Intracellular Therapeutics, Inc., Bristol-Myers Squibb Co., F. Hoffman-La Roche Ind., Pfizer, and Astra-Zeneca and honoraria/consulting fees from Abbott GmbH and Company, AstraZeneca, and Pfizer during the past 3 years.

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  1. Martin Hadamitzky

    Present address: Institute of Medical Psychology and Behavioral Immunobiology, School of Medicine, University Hospital Essen, Hufelandstr. 55, 45122, Essen, Germany

Authors and Affiliations

  1. Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA

    Martin Hadamitzky, Stanley McCunney, Athina Markou & Ronald Kuczenski

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  1. Martin Hadamitzky
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Correspondence to Ronald Kuczenski.

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Hadamitzky, M., McCunney, S., Markou, A. et al. Development of stereotyped behaviors during prolonged escalation of methamphetamine self-administration in rats. Psychopharmacology 223, 259–269 (2012). https://doi.org/10.1007/s00213-012-2713-1

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