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Females develop features of an addiction-like phenotype sooner during withdrawal than males

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Abstract

Rationale

Women meet criteria for substance use disorder after fewer years of drug use than men; this accelerated time course, or telescoping effect, has been observed for multiple drugs, including cocaine. Preclinical findings similarly indicate an enhanced vulnerability in females to developing an addiction-like phenotype; however, it is not yet known if this phenotype develops faster in females versus males.

Objectives

The goal of this study was to determine using a rat model whether two key features of addiction in humans, an enhanced motivation for cocaine and compulsive use, emerge sooner during withdrawal from extended access cocaine self-administration in females versus males.

Methods

Motivation for cocaine, as assessed under a progressive-ratio reinforcement schedule, was determined prior to and following extended access cocaine self-administration (24 h/day, 96 infusions/day, 10 days) and after 7, 14, or 60 days of withdrawal. Compulsive use, or use despite punishment, was evaluated once progressive-ratio responding stabilized by adding histamine, an aversive stimulus, to the cocaine solutions.

Results

Motivation for cocaine increased from baseline sooner during withdrawal in females than males (at 7 versus 14 days); motivation was also highest in the 60-day group. Histamine decreased progressive-ratio responding for cocaine in both sexes, although effects were greatest in males in the 7-day withdrawal group; males reached the female-level of resistance to histamine punishment by 14 days of withdrawal.

Conclusions

Female rats developed addition-like features sooner during withdrawal than male rats indicating that the telescoping effect observed in humans is biologically based. Additionally, like drug-seeking/craving, motivation for cocaine and measures of compulsive use incubate over withdrawal.

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Acknowledgements

This work was supported by NIDA grant R01DA024716 (Lynch).

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Authors and Affiliations

  1. Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, USA

    Eleanor Blair Towers, Anousheh Bakhti-Suroosh & Wendy J. Lynch

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  1. Eleanor Blair Towers
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  2. Anousheh Bakhti-Suroosh
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  3. Wendy J. Lynch
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Correspondence to Eleanor Blair Towers.

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Towers, E.B., Bakhti-Suroosh, A. & Lynch, W.J. Females develop features of an addiction-like phenotype sooner during withdrawal than males. Psychopharmacology 238, 2213–2224 (2021). https://doi.org/10.1007/s00213-021-05846-3

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