Cannabinoid Receptor Blockade Reduces the Opportunity Cost at Which Rats Maintain Operant Performance for Rewarding Brain Stimulation

Abstract

There is ample evidence that blockade of CB1 receptors reduces reward seeking. However, the reported effects of CB1 blockade on performance for rewarding electrical brain stimulation stand out as an exception. By applying a novel method for conceptualizing and measuring reward seeking, we show that AM-251, a CB1 receptor antagonist, does indeed decrease performance for rewarding electrical stimulation of the medial forebrain bundle in rats. Reward seeking depends on multiple sets of variables, including the intensity of the reward, its cost, and the value of competing rewards. In turn, reward intensity depends both on the sensitivity and gain of brain reward circuitry. We show that drug-induced changes in sensitivity cannot account for the suppressive effect of AM-251 on reward seeking. Therefore, the role of CB1 receptors must be sought among the remaining determinants of performance. Our analysis provides an explanation of the inconsistencies between prior reports, which likely arose from the following: (1) the averaging of data across subjects showing heterogeneous effects and (2) the use of methods that cannot distinguish between the different determinants of reward pursuit. By means of microdialysis, we demonstrate that blockade of CB1 receptors attenuates nucleus accumbens dopamine release in response to rewarding medial forebrain bundle stimulation, and we propose that this action is responsible for the ability of the drug to decrease performance for the electrical reward.

Optimal indolence: a normative microscopic approach to work and leisure

“…The neuromodulator dopamine is of particular interest. Previous macroscopic analyses from pharmacological and drugs of addiction studies have revealed that an increase in the tonic release of the neuromodulator dopamine shifts the three-dimensional relationships towards longer prices [21][22][23], as if, for instance, dopamine multiplies the intensity of the reward. Equally, models of instrumental vigour have posited that tonic dopamine signals the average reward rate, thus realizing the opportunity cost of time [24,67,68].…”

“…This decision has been studied by economists [1][2][3][4][5], behavioural psychologists [6][7][8][9][10][11][12][13][14][15][16], ethologists [17] and neuroscientists [18][19][20][21][22][23][24]. Tasks involving free-operant behaviour are particularly revealing, because subjects can choose what, when and how, minimally encumbered by direct experimenter intervention.…”

Psychophysical inference of frequency-following fidelity in the neural substrate for brain stimulation reward

“…The model and associated three-dimensional (3D) measurement strategy have been used in previous studies to differentiate between actions of experimental manipulations on early and late stages of reward processing [21][22][23][24][25][26][27]. In the early versions of the model, perfect frequency following was assumed.…”

Role of Dopamine Tone in the Pursuit of Brain Stimulation Reward

“…In the cases of rats GBR11-GBR14, each drug session included a complete survey of the mountain. In these cases, the data were resampled by survey (Hernandez et al, 2010;Trujillo-Pisanty et al, 2011). For example, 10 drug sessions were run with rat GBR11.…”

“…ICSS is typically measured in the curve-shift (Edmonds and Gallistel, 1974;Edmonds and Gallistel, 1977;Miliaressis et al, 1986) or progressive-ratio (Hodos, 1961) paradigm. It has been demonstrated recently (Arvanitogiannis and Shizgal, 2008;Hernandez et al, 2010;Trujillo-Pisanty et al, 2011) that neither method provides sufficient isolation of the different processes underlying reward seeking to distinguish between competing hypotheses concerning the variables to which dopamine neurons contribute, which include the sensitivity and gain of brain reward circuitry (Hernandez et al, 2010) and subjective effort cost (Salamone et al, 2005;Niv et al, 2007).…”