Abstract
Mesolimbic dopamine (DA) is involved in behavioral activation and effort-related processes. Rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements, and instead select less effortful food-seeking behaviors. In the present study, the effects of several drug treatments were assessed using a progressive ratio (PROG)/chow feeding concurrent choice task. With this task, rats can lever press on a PROG schedule reinforced by a preferred high-carbohydrate food pellet, or alternatively approach and consume the less-preferred but concurrently available laboratory chow. Rats pass through each ratio level 15 times, after which the ratio requirement is incremented by one additional response. The DA D2 antagonist haloperidol (0.025–0.1 mg/kg) reduced number of lever presses and highest ratio achieved but did not reduce chow intake. In contrast, the adenosine A2A antagonist MSX-3 increased lever presses and highest ratio achieved, but decreased chow consumption. The cannabinoid CB1 inverse agonist and putative appetite suppressant AM251 decreased lever presses, highest ratio achieved, and chow intake; this effect was similar to that produced by pre-feeding. Furthermore, DA-related signal transduction activity (pDARPP-32(Thr34) expression) was greater in nucleus accumbens core of high responders (rats with high lever pressing output) compared to low responders. Thus, the effects of DA antagonism differed greatly from those produced by pre-feeding or reduced CB1 transmission, and it appears unlikely that haloperidol reduces PROG responding because of a general reduction in primary food motivation or the unconditioned reinforcing properties of food. Furthermore, accumbens core signal transduction activity is related to individual differences in work output.
Highlights
Brain dopamine (DA), in nucleus accumbens, plays an important role in regulating aspects of instrumental behavior [1,2,3,4]
There was a tendency for animals that had high vehicle rates of responding, and correspondingly low vehicle levels of chow intake, to show increases in chow intake with haloperidol; this was marked by a significant correlation between vehicle number of lever presses and the difference in chow consumption between vehicle and the highest dose of haloperidol (r = 0.69, df = 30, p,0.05)
The partial correlation between lever pressing and chow intake that controlled for between-subject variability was statistically significant (20.557, df = 125, p,0.001), indicating that the inverse relation between lever pressing and chow intake was evident across treatments even if one controlled for the between-subject variability in lever pressing
Summary
Brain dopamine (DA), in nucleus accumbens, plays an important role in regulating aspects of instrumental behavior [1,2,3,4]. T-maze and lever pressing versions of effort discounting procedures have demonstrated that DA antagonism shifts choice behavior of rats towards low effort alternatives [23,24] Another task that has been used is the concurrent fixed-ratio 5 (FR5)/chow feeding procedure, in which rats can either lever press on a FR5 schedule for preferred high-carbohydrate food pellets, or approach and consume less-preferred rodent chow that is freely available in the chamber [1,6,25]. Systemic or intraaccumbens administration of DA antagonists and accumbens DA depletions shift response allocation such that lever pressing is decreased but chow intake is substantially increased [6,25,26,27,28,29,30,31] This effect is not due to drug-induced changes in food preference or consumption [6,28]. The effects induced by DA antagonism or depletion differ substantially from those seen following pre-feeding [6] or treatment with appetite suppressant drugs such as fenfluramine [25] or cannabinoid CB1 antagonism [30]; these appetite-related manipulations failed to increase chow intake at doses that suppress lever pressing
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
