Trends in Pharmacological Sciences
ReviewInsights from Preclinical Choice Models on Treating Drug Addiction
Section snippets
Drug Addiction
Drug addiction is an insidious and global public health problem. Estimates from the most recent World Drug Report indicate that 246 million adults aged 15–64 have used at least one illicit drug within the past year and, since 2008, this number of individuals has increased year on year [1]. Although both scientists and clinicians agree that drug addiction is a significant public health issue, there are disagreements regarding the operational definition of drug addiction 2, 3. For example, both
Preclinical Drug Choice
The development of preclinical drug self-administration procedures has been critical for improving our understanding of substance-use disorders. All drug self-administration procedures are founded on the principles of operant conditioning related to the three-term contingency [13] as follows (Equation 1):where SD denotes the discriminative stimulus (see Glossary), R denotes the response by the organism, and SC denotes the consequent stimulus. For example, in a simple type of drug
Concurrent Availability of an Alternative Reinforcer
To date, preclinical drug versus nondrug choice procedures have been established for the abused drugs cocaine 20, 21, 22, methamphetamine 23, 24, 3,4-methylenedioxymethamphetamine [25], heroin 26, 27, remifentanil [28], secobarbital and chlordiazepoxide [29], and nicotine [30] in either nonhuman primates or rats. With the exception of one heroin versus electrical brain stimulation choice study [31], all other preclinical drug versus nondrug choice procedures have used some food variant as the
Pharmacological Determinants
One area of scientific discovery where preclinical choice procedures have emerged as having translational utility is in the development and evaluation of candidate pharmacotherapies for substance-use disorders. Examples of recent pharmacological variables that have either decreased or increased drug versus food choice are listed in Table 1. Preclinical drug versus food choice procedures evaluating subchronic pharmacological treatments have produced concordant results with both human laboratory
Biological Determinants
Emerging preclinical evidence has implicated sex as a biological determinant of both substance-use initiation and progression to substance-use disorders (recently reviewed in 100, 101). The role of sex as a determinant of preclinical drug versus nondrug choice has been recently investigated in both rats 65, 102, 103, 104 and monkeys [105], and these results suggest two main findings. First, there was no effect of estrous cycle on intravenous cocaine versus food choice in rats or an effect of
Concluding Remarks
Substance-use disorders occur in the context of numerous competing alternative nondrug reinforcers. The diagnosis of substance-use disorders is founded in part on the maladaptive allocation of behavior toward drug use at the expense of other more adaptive behaviors maintained by nondrug alternative reinforcers. This diagnosis implies that the treatment of substance-use disorders seeks not only to decrease behaviors maintained by the abused substance, but also to increase behaviors maintained by
Acknowledgments
The authors’ research related to this topic has been supported by the National Institute on Drug Abuse of the National Institutes of Health under award numbers R01DA031718 (M.L.B.), R01DA033364 (M.L.B. and S.S.N.), and R01DA026946 (S.S.N.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We also acknowledge the artistic assistance of Megan Jo Moerke.
Glossary
- Concurrent schedule of reinforcement
- one category of reinforcement schedules where two different schedules of reinforcement are presented to the organism simultaneously or concurrently. Responding on one operant manipulandum to obtain one of the concurrently available reinforcers implies a ‘choice’ and subsequent forfeiture of the other reinforcer available during that particular experimental trial or session.
- Consequent stimulus (SC)
- one category of stimuli in operant terminology; defined as a
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Shifts in stimulus control over opioid use with increasing periods of recovery
2024, Pharmacology Biochemistry and BehaviorNeural circuits controlling choice behavior in opioid addiction
2023, NeuropharmacologyCitation Excerpt :For example, dosing of rhesus monkeys with the lesser-known MOR antagonist methocinnamox (MCAM) decreases heroin self-administration and remifentanil choice, while shifting choice toward natural reward (i.e. food) (Maguire et al., 2019). Additionally, KOR agonists, specifically MOR/KOR mixed therapeutics, reduce the reinforcing effects, and subsequently the self-administration, of opioids (Banks and Negus, 2017). One study reported that when combined with self-administered oxycodone, the KOR agonists salvinorin A and nalfurafine, reduced taking of oxycodone in male rhesus monkeys (Zamarripa et al., 2020).
Demand and cross-price elasticity of cocaine and social contact in a free-operant procedure of nonexclusive choice
2023, Pharmacology Biochemistry and BehaviorCitation Excerpt :Analysis of cross-price elasticity and the substitutability of commodities can inform clinical interventions (e.g., by detailing how changes in the consumption of one good or variations in its cost may alter behavioral allocation to another in support of targeted interventions or intervention sequencing). This approach also recognizes that the value of a commodity is often determined by environmental factors like concurrently available reinforcers and better matches ecological-relevant conditions in which choices are not mutually exclusive (Banks and Negus, 2017; Smith and Beckmann, 2021; Strickland, 2022). Analysis of cross-price elasticity revealed that a social partner, regardless of the partner's exposure to cocaine, is a reliable economic substitute for cocaine.
Sensitivity of a fentanyl-vs.-social interaction choice procedure to environmental and pharmacological manipulations
2022, Pharmacology Biochemistry and BehaviorEffects of environmental manipulations on cocaine-vs-social choice in male and female rats
2022, Pharmacology Biochemistry and Behavior