Dopaminergic Modulation of Effort-Related Choice Behavior as Assessed by a Progressive Ratio Chow Feeding Choice Task: Pharmacological Studies and the Role of Individual Differences

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.

Opioidergic and dopaminergic modulation of cost/benefit decision-making in Long Evans Rats

“…Experiment 1 demonstrated that the DA D 2 receptor antagonist haloperidol, at both doses tested, decreased the breakpoint, number of lever presses, number of reinforcers obtained, and increased intake of freely available laboratory chow. Our results are in line with previous work that has carefully described the role of DA mechanisms on this lever pressing and chow feeding task [52,53,58]. DA antagonism and striatal depletions by 6-OHDA or tetrabenazine have been shown to decrease measures of lever pressing while resulting in compensatory increases in chow intake.…”

“…Saline served as the vehicle control for all naloxone experiments. Doses of haloperidol and naloxone were selected from previously published data [52][53][54][55]. All injections were delivered intraperitoneally (IP).…”

“…The basic decision-making task was adapted and modified from those created by Salamone and colleagues [53]. Operant sessions were conducted in two-lever operant chambers (27 cm length x 30 cm width x 29 cm height; Med-Associates, St. Albans City, VT).…”

Dissociable Contributions of Anterior Cingulate Cortex and Basolateral Amygdala on a Rodent Cost/Benefit Decision-Making Task of Cognitive Effort

“…Regions deemed inessential in physical effort (eg, the prefrontal cortex; Walton et al, 2003b) have been shown to have a prominent role in human cognitive effort Schmidt et al, 2012). Furthermore, these human studies have emphasized how individual differences in brain function influence individual differences in effort expenditure (Treadway et al, 2012b), an examination all but absent from animal effort literature (but see Randall et al, 2012).…”

What’s Special about the Ethical Challenges of Studying Disorders with Altered Brain Activity?

“…However, there can be barriers for making such a switch: most importantly, to introduce the use of high incentive rewards would increase the behavioural baseline response. The incentive value of rewards as demonstrated behaviourally is known to be significantly affected by quite minor changes to experimental procedure such as a change in the reinforcer in use (Randall et al 2012). Behavioural analyses of reinforcement-value measure responding on schedules requiring animals to make progressively more and more responses (such as pressing a lever within a Skinner box) to secure the same level of food reward.…”