Gender and stimulus difference in cue-induced responses in abstinent heroin users

Abstract

Background

Environmental stimuli associated with drug taking have been known to elicit drug craving and increase the likelihood of relapse, and sex differences have been observed in the development of drug addiction and relapse to drug taking. Differential cue paradigms (drug-related imagery scripts and drug-related paraphernalia) have been used to investigate cue-induced drug craving. However, there is little research on the possible gender differences in responses to drug cues in heroin-dependent individuals. This study examined whether two different stimuli, drug-related imagery scripts and drug-related paraphernalia, produce similar or different patterns of cue reactivity in heroin-dependent men and women.

Methods

In the laboratory sessions, 26 male and 23 female heroin-dependent subjects were exposed to script-guided imagery of heroin-related cue situations and to heroin-related paraphernalia (e.g., needles, syringes, spoons, cigarette filters, and aluminum foil). Heroin craving, subjective anxiety, emotion state ratings, and cardiovascular changes were assessed.

Results

Significant increases in heroin craving were seen with drug-imagery scripts or drug paraphernalia but not with neutral-relaxing imagery or neutral-item handling. In addition, drug imagery and paraphernalia produced significant increases in subjective anxiety, negative emotions, systolic and diastolic blood pressure, and heart rate, as well as decreases in positive emotion. Paraphernalia exposure was somewhat more effective than imagery scripts in inducing heroin craving, primarily reflecting a lower response to imagery scripts among men. Most other dependent measures also differed by gender, and each gender difference occurred with imagery scripts only or with paraphernalia only.

Conclusions

The present results indicate that heroin-imagery scripts and heroin paraphernalia each induce heroin craving and emotional and cardiovascular changes, but that the changes show a complex pattern of gender differences that may need to be taken into account in future laboratory studies.

Introduction

Drug addiction is characterized by high rates of relapse and long-lasting vulnerability to drug-taking behaviors (Mendelson and Mello, 1996, O'Brien, 1997). Drug-associated environmental cues are among the factors that have been shown to reinstate drug-seeking and drug-taking in laboratory animals and to induce drug craving in humans (Lu et al., 2003, See, 2002, Shaham et al., 2003, Sinha et al., 2000). Drugs for which cues can increase subjective craving and autonomic arousal in humans include cocaine (Ehrman et al., 1992, Foltin and Haney, 2000), methamphetamine (Newton et al., 2006), opiates (Childress et al., 1994, O'Brien et al., 1992), nicotine (Chiamulera, 2005), and alcohol (Drummond et al., 1990).

Different studies have used different types of drug-associated cues. For example, imagery-based drug-related cues have been developed by having subjects identify a recent situation that was a trigger for subsequent drug use (e.g. buying drugs, being at a bar, or watching others use drugs) (Lang et al., 1980, Sinha et al., 2000, Tiffany and Drobes, 1990). Such cues have been demonstrated to elicit drug craving and physical responses (Sinha et al., 2000, Tiffany and Drobes, 1990). Alternatively, subjects may be given the opportunity to handle drug-related paraphernalia, such as needles, syringes, spoons, cigarette filters, or aluminum foil; this, too, produces a strong urge to use drug, which may be associated with conditioned drug-like or drug-opposite effects (Childress et al., 1993, Powell, 1995, Robbins et al., 1999, Satel et al., 1995).

Evidence is accumulating that the physiology and epidemiology of drug abuse differ somewhat between males and females (Carroll et al., 2004, Lynch et al., 2002). Females appear to be more vulnerable than males to the reinforcing effects of psychostimulants, opiate, and nicotine during many phases of the addiction process. In human studies, it is reported that women substance users typically begin using substances later than do men, but they demonstrate an accelerated transition from casual, controlled use to uncontrolled, “binge” patterns of use (Kosten et al., 1996, Lynch et al., 2002, Westermeyer and Boedicker, 2000). Also, female drug users are more likely to report subjective distress before and after the onset of drug abuse, whereas male abusers often report depression after use of substances (Brady and Randall, 1999, Kosten et al., 1993, Sinha and Rounsaville, 2002). Of particular relevance to the present study is that female cocaine addicts were more likely to report increased craving in response to cues than males (Robbins et al., 1999). However, there is little known on the gender effect of cue response in heroin addicts. Such differences, if not accounted for, may be partly responsible for difficulties in translating laboratory findings (Lu et al., 2003, O'Brien, 2005, Shaham et al., 2003) into the development of effective anti-craving and relapse-prevention medications (O'Brien, 2005, Vocci et al., 2005).

The purpose of the present paper is to examine whether heroin-dependent men and women show similar responses to different heroin-related cues. All subjects were participating in inpatient treatment and had abstained from heroin and other drugs for at least 3 weeks. All were exposed to the same set of laboratory stimuli. Stimuli included heroin-related paraphernalia (e.g., syringes, spoons, cigarette filters, and aluminum foil) and drug-related imagery. Self-reported levels of heroin craving and general emotional states were assessed before and after each exposure to the cues. Physiological recording of heart rate and blood pressure occurred continuously throughout the cue-exposure session.