Sex differences in effort-related decision-making: role of dopamine D2 receptor antagonism

Abstract

Rationale

Depressed individuals demonstrate debilitating symptoms, including depressed mood, anhedonia, and effort-related deficits. Effort-related decision-making can be measured through providing subjects with a choice between high effort/reward and low effort/reward options, which is a dopamine (DA)–dependent behavior. While previous research has shown sex differences in depression rates, this has not been examined within operant-based effort-related decision-making tasks nor has DA been shown to underlie this behavior in female rats.

Objectives

The current study investigated sex differences in an effort-related decision-making task prior to and following administration of the DA D2 receptor antagonist haloperidol (HAL).

Methods

Adult rats were food restricted or fed freely and trained in an effort-related progressive ratio choice task. After stable responding, HAL was administered acutely (0.05–0.2 mg/kg) prior to testing.

Results

Results indicate a significant effect of sex on training variables, with males having a greater number of lever presses, higher ratios, and longer active lever times. Pretreatment with HAL significantly reduced the same measures in both sexes for the high-valued reward, while increasing chow consumption in the food restricted males. Food restricted rats showed a greater number of total lever presses and achieved higher ratios; however, the effect in male food restricted rats was greatest.

Conclusions

These data suggest that, although there are sex differences in training, HAL decreases behavior across sexes, demonstrating that the D2 mechanism is similar in both sexes. These findings provide a better understanding of motivational dysfunction in both sexes and potential treatment targets for depression.

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Correspondence to Leslie Matuszewich.

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Errante, E.L., Chakkalamuri, M., Akinbo, O.I. et al. Sex differences in effort-related decision-making: role of dopamine D2 receptor antagonism. Psychopharmacology (2021). https://doi.org/10.1007/s00213-021-05795-x

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Keywords

  • Motivation
  • Reward
  • Depression
  • Sex differences
  • Dopamine
  • D2 receptor
  • Food restriction
  • Behavioral activation