%0 Journal Article
%T Pharmacological characterization of sex differences in the effects of dopaminergic drugs on effort-based decision making in rats.
%A Ecevitoglu A
%A Beard KR
%A Srynath S
%A Edelstein GA
%A Olivares-Garcia R
%A Martinez-Verdu A
%A Meka N
%A Correa M
%A Salamone JD
%J Psychopharmacology (Berl)
%V 0
%N 0
%D 2024 Jun 6
%M 38842701
%F 4.415
%R 10.1007/s00213-024-06615-8
%X <B>BACKGROUND: </B>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.<BR><B>OBJECTIVE: </B>Previous rodent studies mainly employed male rats, and it is imperative to conduct studies in male and female rats.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.