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Pharmacological characterization of sex differences in the effects of dopaminergic drugs on effort-based decision making in rats.
- Source :
- Psychopharmacology; Oct2024, Vol. 241 Issue 10, p2033-2044, 12p
- Publication Year :
- 2024
-
Abstract
- Rationale: Motivational dysfunctions related to effort exertion are common in psychiatric disorders. Dopamine systems regulate exertion of effort and effort-based choice in humans and rodents. Objectives: Previous rodent studies mainly employed male rats, and it is imperative to conduct studies in male and female rats. Methods: The present studies compared the effort-related effects of IP injections of the dopamine antagonists ecopipam and haloperidol, and the vesicular monoamine transport-2 inhibitor tetrabenazine (TBZ), in male and female rats using the fixed ratio 5/chow feeding choice task. Results: Ecopipam (0.05–0.2 mg/kg) and haloperidol (0.05–0.15 mg/kg) induced a low-effort bias, decreasing lever pressing and increasing chow intake in males and females in the same dose range. With lever pressing, there was a modest but significant dose x sex interaction after ecopipam injection, but there was no significant interaction after administration of haloperidol. In the first study with TBZ (0.25-1.0 mg/kg), there was a robust sex difference. TBZ shifted choice from lever pressing to chow intake in male rats, but was ineffective in females. In a second experiment, 2.0 mg/kg affected choice behavior in both males and females. TBZ increased accumbens c-Fos immunoreactivity in a sex-dependent manner, with males significantly increasing at 1.0 mg/kg, while females showed augmented immunoreactivity at 2.0 mg/kg. Conclusions: The neural and behavioral effects of TBZ differed across sexes, emphasizing the importance of conducting studies in male and female rats. This research has implications for understanding the effort-related motivational dysfunctions seen in psychopathology. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00333158
- Volume :
- 241
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Psychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 180004481
- Full Text :
- https://doi.org/10.1007/s00213-024-06615-8