Effort-related motivational effects of methylphenidate: Reversal of the low-effort bias induced by tetrabenazine and enhancement of progressive ratio responding in male and female rats.
Alev Ecevitoglu, Renee A Rotolo, Gayle A Edelstein, Alexandra Goldhamer, Matthew Mitola, Rose E Presby, Abigail Yu, Deanna Pietrorazio, Emma Zorda, Merce Correa, John D Salamone
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Abstract
Dopamine (DA) regulates behavioral activation and effort-related aspects of motivation. Blockade of DA storage by tetrabenazine (TBZ) induces depressive symptoms in humans, including fatigue and apathy. TBZ shifts choice behavior in rodents from high-effort to low-effort options, which can be used to model motivational symptoms observed in psychiatric disorders. The catecholamine transport inhibitor methylphenidate (MPH) reverses the effort-related effects of TBZ in male rats, but this effect needs to be investigated in females. The current study examined the effects of MPH on effort-based choice in male and female rats. Animals were tested on the fixed ratio 5 (FR5)/chow feeding choice task. Because of sex differences in the effects of TBZ, 1.0 mg/kg was used in males, while 2.0 mg/kg was used in females. In both sexes, TBZ shifted choice from lever pressing to chow intake. Co-administration of MPH reversed the effort-related effects of TBZ in males at all doses tested (0.5-4.0 mg/kg IP), whereas only 1.0 and 2.0 mg/kg MPH reversed the effects of TBZ in females. Rats also were tested on a progressive ratio (PROG) schedule and a PROG/chow feeding choice task to assess the effects of MPH administered alone (0.5-4.0 mg/kg IP). MPH increased high-effort PROG responding on both tasks in males, whereas females showed no significant increase in lever pressing across the dose range tested. Investigating sex differences in the pharmacology and neurochemistry of effort-based choice enhances our understanding of sex as a factor in motivational dysfunctions, and may foster the development of treatments for effort-related psychiatric symptoms.
期刊介绍：
Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).
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