Supply of a Nondrug Substitute Reduces Escalated Heroin Consumption

Abstract

Escalation of drug consumptionFa hallmark of addictionFhas been hypothesized to be associated with a relative devaluation of alternative nondrug rewards and thus with a decrease in their ability to compete with or to substitute for the drug. In a behavioral economic framework, decreased substitutability of nondrug rewards for drug would explain why drug consumption is behaviorally dominant and relatively resistant to change (eg price-inelastic) in drug-addicted individuals. The goal of the present study was to test this hypothesis using a validated rat model of heroin intake escalation. Escalation was precipitated by long (6 h, long access (LgA)), but not short (1 h, short access (ShA)), daily access to i.v. heroin self-administration. After escalation, the effects of price (ie fixed-ratio value) on heroin consumption were assessed under two alternative reward conditions: in the presence or absence of a nondrug substitute for heroin (ie four freely available chow pellets). As expected, escalated heroin consumption by LgA rats was less sensitive to price than heroin consumption by ShA rats, showing that heroin had acquired greater reinforcing strength during escalation. However, supplying a substitute during access to heroin was sufficient to reverse this post-escalation increase in the reinforcing effectiveness of heroin. Thus, escalated heroin consumption is not associated with a decreased sensitivity to competing nondrug rewards. Escalated drug use may therefore persist, not so much because of a relative devaluation of nondrug substitutes, but because of a loss or reduction of their availability.

Reward comparison: the Achilles’ heel and hope for addiction

“…In general, it appears that all natural rewards can be protective. Drug self-administration is reduced by the availability of a sweet such as saccharin or a glucose + saccharin mixture [83][84][85]. Drug self-administration is reduced by the availability of a running wheel, particularly in females [86].…”

“…Environmental enrichment also is protective in rats when provided during adulthood alone [90]. Sweets and even chow are protective when presented in adulthood concurrent with the opportunity to self-administer drug [83][84][85]. Finally, the sweets need not be concurrently available to be protective in adult rats.…”

Compulsive drug use and its neural substrates

“…Consistent with the notion that escalation of drug intake is an important step in the development of compulsive drug use, it has been shown that, after escalated cocaine or alcohol self-administration, other behavioral characteristics of addictive behavior can also be observed. These include increased motivation for the drug (Paterson and Markou, 2003;Liu et al, 2005;Lenoir and Ahmed, 2008;Wee et al, 2008;Orio et al, 2009), increased sensitivity for reinstatement of drug seeking after extinction (Mantsch et al, 2004;Ahmed and Cador, 2006;Kippin et al, 2006;Knackstedt and Kalivas, 2007) and reduced sensitivity to punishment (Wolffgramm, 1991;Wolffgramm andHeyne, 1991, 1995;H ö lter et al, 1998;Spanagel and H ö lter, 1999;Vanderschuren and Everitt, 2004;Lesscher et al, 2010;Ahmed, 2012).…”

Parsing the addiction phenomenon: Self-administration procedures modeling enhanced motivation for drug and escalation of drug intake

“…As illustrated in figure 1C [35], the daily number of infusions that are self-administered by animals given short-access (i.e., 1 hour; ShA) to cocaine remained stable over 12 days (filled circles); whereas, when given long access (i.e., 6 hours) to cocaine the daily number of self-administered infusions drastically increased over 12 days (open circles). The observation of escalated rates of drug-intake after long-access training is a highly replicable phenomenon that has been documented to occur for several drugs of abuse including cocaine [35], methamphetamine [37] and heroin [38]. Many different laboratories are beginning to use this long-access training procedure in order to study the neurobiological [39,40,41] and behavioral [42,43] consequences of a history of escalated cocaine intake.…”