Intranasal cocaine functions as reinforcer on a progressive ratio schedule in humans

Abstract

Cocaine dependence continues to be a worldwide public health concern. Although the majority of individuals reporting cocaine use do so via the intranasal route, relatively few laboratory experiments have examined the reinforcing effects of cocaine administered intranasally. The purpose of this experiment was to measure the reinforcing effects of intranasal cocaine using a progressive ratio schedule in which eight cocaine-using subjects chose between doses of cocaine (4 [placebo], 15, 30 and 45 mg) and an alternative reinforcer ($0.25). During each session, subjects first sampled the dose of cocaine available that day and then made six choices between that dose and money, which were available on concurrent progressive ratio schedules of responding. Break points for active cocaine doses were higher than those for placebo but no statistically significant active versus placebo dose effects were observed on subject-rated or physiological measures. These data demonstrate that intranasal cocaine functions as a reinforcer under a progressive ratio schedule in humans. Future research should test higher cocaine doses and larger values of the alternative reinforcer. These procedures may be useful for examining the influence of putative pharmacological and behavioral interventions on intranasal cocaine self-administration.

Introduction

Cocaine dependence continues to be a significant public health concern worldwide. Data from the United States indicate that approximately 2 million Americans over the age of 12 report current cocaine use (Substance Abuse and Mental Health Services Administration [SAMHSA], 2009). In the European Union, it is estimated that 1.5 million people report current cocaine use (European Monitoring Centre for Drugs and Drug Addiction [EMCDDA], 2009). Importantly, despite prevention and intervention efforts, prevalence of cocaine use remains stable (e.g., SAMHSA, 2009). Moreover, cocaine use has come to be associated with a host of mental and physical health problems (for reviews see Chen and Lin, 2009, Cregler, 1989). While the use of smoked cocaine (i.e., crack) has received much of the focus of epidemiological research (e.g., Substance Abuse and Mental Health Services Administration, 2005, Substance Abuse and Mental Health Services Administration, 2007), it is important to recognize that a significant number of cocaine users in the United States and Europe do not smoke cocaine (up to 2/3 of cocaine users; Foltin and Haney, 2004; c.f., Gossop et al., 1994, Prinzleve et al., 2004). In addition, many report their initial experience with cocaine to be via intranasal insufflation (Foltin and Haney, 2004, Gorelick, 1992, van der Meer Sanchez and Nappo, 2007).

The pharmacodynamic effects of cocaine have been studied extensively following oral, intranasal, smoked and intravenous administration in humans (e.g., Fischman, 1984, Foltin et al., 1988, Foltin et al., 1990, Rush et al., 1999). Cocaine occupies the dopamine transporter regardless of route, which produces increases in positive subjective drug effects, heart rate and blood pressure, but with different rates of onset observed as a function of route of administration (Foltin and Fischman, 1991, Oliveto et al., 1995, Resnick et al., 1977, Volkow et al., 2000). The reinforcing effects of cocaine have also been demonstrated under a number behavioral arrangements (e.g., drug versus alternative reinforcer choice, drug versus placebo choice, multiple choice procedure, fixed ratio and progressive ratio schedules), but primarily with smoked or intravenous administration (Donny et al., 2004, Fischman and Schuster, 1982, Haney et al., 1998, Haney et al., 2006, Hart et al., 2007, Sobel et al., 2004, Walsh et al., 2010). The reinforcing effects of intranasal cocaine have not been examined as extensively and have mainly been studied using choice procedures (Higgins et al., 1994, Lile et al., 2004, Rush et al., 2010, Stoops et al., 2010).

The purpose of this experiment was to determine the reinforcing effects of a range of doses of intranasal cocaine (4 [placebo], 15, 30 and 45 mg) on a progressive ratio schedule of responding because cocaine is used intranasally by a significant number of individuals throughout the world and the reinforcing effects of intranasal cocaine have been examined under limited conditions. We hypothesized that cocaine would function as a reinforcer (i.e., engender higher break points than placebo). To more fully characterize the effects of intranasal cocaine, a battery of subject-rated and physiological measures was included.