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Pharmacological characterization of sex differences in the effects of dopaminergic drugs on effort-based decision making in rats.
Ecevitoglu, Alev; Beard, Kathryn R; Srynath, Sonia; Edelstein, Gayle A; Olivares-Garcia, Regulo; Martinez-Verdu, Andrea; Meka, Nicolette; Correa, Merce; Salamone, John D.
Afiliación
  • Ecevitoglu A; Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA.
  • Beard KR; Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA.
  • Srynath S; Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA.
  • Edelstein GA; Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA.
  • Olivares-Garcia R; Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA.
  • Martinez-Verdu A; Àrea de Psicobiologia, Universitat Jaume I, Campus de Riu Sec, Castelló, 12071, Spain.
  • Meka N; Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA.
  • Correa M; Àrea de Psicobiologia, Universitat Jaume I, Campus de Riu Sec, Castelló, 12071, Spain.
  • Salamone JD; Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA.
Psychopharmacology (Berl) ; 241(10): 2033-2044, 2024 Oct.
Article en En | MEDLINE | ID: mdl-38842701
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tetrabenazina / Antagonistas de Dopamina / Relación Dosis-Respuesta a Droga / Haloperidol Límite: Animals Idioma: En Revista: Psychopharmacology (Berl) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tetrabenazina / Antagonistas de Dopamina / Relación Dosis-Respuesta a Droga / Haloperidol Límite: Animals Idioma: En Revista: Psychopharmacology (Berl) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania