Effects of Oral and Intravenous Administration of Buspirone on Food–Cocaine Choice in Socially Housed Male Cynomolgus Monkeys

Abstract

Drugs acting at D 3 dopamine receptors have been suggested as medications for cocaine dependence. These experiments examined the effects of intravenously and orally administered buspirone, a D2-like receptor antagonist with high affinity for D 3 and D 4 receptors, on the relative reinforcing strength of cocaine in group-housed male cynomolgus monkeys. Use of socially housed monkeys permitted the assessment of whether social status, known to influence D2-like receptor availability, modulates the behavioral effects of buspirone. Buspirone was administered acutely to monkeys self-administering cocaine under a food-drug choice procedure in which a cocaine self-administration dose-effect curve was determined daily. When administered by either route, buspirone significantly decreased cocaine choice in dominant-ranked monkeys. In subordinate monkeys, however, i.v. buspirone was ineffective on average, and oral buspirone increased choice of lower cocaine doses. The effects of buspirone only differed according to route of administration in subordinate monkeys. Moreover, it is noteworthy that the effects of buspirone were similar to those of the D 3 receptor-selective antagonist PG01037 and qualitatively different than those of less selective drugs that act at D2-like or serotonin (5-HT) 1A receptors, suggesting a D 3 and possibly D 4 receptor mechanism of action for buspirone. Taken together, the data support the utility of drugs targeting D 3 /D 4 receptors as potential treatments for cocaine addiction, particularly in combination with enriching environmental manipulations.

Making the Case for ‘Power Abuse Disorder' as a Nosologic Entity

“…Cocaine as (1) a dopamine transport inhibitor and, hence, an enhancer of extracellular dopamine in mesocorticolimbic brain regions, as well as (2) a drug of abuse with high abuse liability, seems an excellent tool to test (a) the consequences of the well-documented dominance-induced increase in D2/D3 receptors in reward neuronetworks with respect to the sensitivity of the power-wielding individual to reward in general and (b) with respect to the increased risk of PADed individuals for cocaine dependence, a comorbidity that seems well known anecdotally and which the findings in female cynomolgous monkeys [8] and male Lister Hooded rats [11] seem to support. Nader and coworkers have already contributed a great deal of data obtained in a food-cocaine choice experimental paradigm suggesting, in our interpretation, that, overall, the sensitivity to physiological stimuli (i.e., palatable food pellets) is not changed by the acquisition of power/social dominance [8,71,102]. Respective data obtained from widely used and easily accessible experimental paradigms and species (e.g., CPP/CPA in C57BL/6J mice or Sprague Dawley rats) would be desirable.…”

Evaluation of the “Pipeline” for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research

“…for 5 days) was ineffective overall in altering food-cocaine choice. One study was conducted in group-housed cynomolgus monkeys and one involved rhesus monkeys (Czoty and Nader, 2015;John et al, 2015, respectively). Interestingly, in the former study, buspirone decreased cocaine choice in socially dominant monkeys, suggesting that the efficacy of buspirone might be enhanced in enriched environments.…”

Multi-Atlas Library for Eliminating Normalization Failures in Non-Human Primates

“…Briefly, the animals were sedated with 10-15 mg/kg ketamine and transported to the MRI Center where anesthesia was maintained via inhaled 1.5-3% isoflurane (Czoty and Nader 2015; Czoty et al 2013; Czoty and Nader 2012). The animals were artificially ventilated to control physiological parameters across animals.…”