A drug-vs-food “choice” self-administration procedure in rats to investigate pharmacological and environmental mechanisms of substance use disorders

Townsend, E. Andrew; Schwienteck, Kathryn L.; Lawson, Stephen T.; Banks, Matthew L.

doi:10.1016/j.jneumeth.2021.109110

Cited by 37 publications

(59 citation statements)

References 74 publications

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“…Both cocaine-and heroin-maintained dose-dependent increases in choice over a nondrug food alternative reinforcer in rhesus monkeys. The present results are consistent with the extant literature using both nonhuman primates (Czoty et al, 2005;Foltin et al, 2015;Nader & Woolverton, 1991;Woolverton & Balster, 1979) and rats (Beckmann et al, 2019;Thomsen et al, 2013;Townsend, Schwienteck, et al, 2021) demonstrating the feasibility of establishing drug choice over a nondrug alternative reinforcer. Moreover, these preclinical data are consistent with human laboratory studies demonstrating dose-dependent drug-vs-money choice for both cocaine and opioids (Brandt et al, 2020;Hart et al, 2000;Lile et al, 2016).…”

Section: Discussionsupporting

confidence: 91%

Contextual extinction of drug-associated discriminative stimuli fails to attenuate drug-vs-food choice in rhesus monkeys

Banks

Hutsell

Negus

2019

Preprint

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Background: In drug addiction, relapse can be triggered by cues that function as discriminative stimuli to signal contingencies of drug availability and promote drug-taking behavior. Extinction procedures can weaken the association between drug-associated cues and drug use and may reduce the probability of relapse. This study evaluated effects of a regimen of extinction training on cocaine self-administration maintained in rhesus monkeys under a cocaine-vs.-food choice procedure that has been used previously to evaluate effectiveness of other candidate treatments for cocaine abuse.Methods: Behavior was initially maintained under a concurrent schedule of food delivery (1-g food pellets; fixed-ratio 100 schedule) and cocaine injections (0-0.1 mg/kg/injection; fixed-ratio 10 schedule) during daily 2-h choice sessions in male rhesus monkeys (n=4). Subsequently, choice sessions were supplemented by daily 20-h extinction sessions for 14 consecutive days.During extinction sessions, cocaine-associated discriminative stimuli were presented, but responding did not produce cocaine injections. Cocaine continued to be available during choice sessions.Results: Prior to extinction, cocaine maintained a dose-dependent increase in cocaine vs. food choice. Responding during extinction sessions declined to low levels by the fifth day. Exposure to extinction sessions produced a more gradual but significant decline in cocaine choice and a complementary increase in food choice during choice sessions.Conclusions: These preclinical results support the effectiveness of extinguishing cocaineassociated discriminative stimuli as a non-pharmacological treatment strategy for reducing cocaine choice. Moreover, these results also support the construct validity of preclinical drug vs.food choice procedures as a tool for candidate treatment evaluation for cocaine addiction.

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Section: Discussionsupporting

confidence: 91%

Contextual extinction of drug-associated discriminative stimuli fails to attenuate drug-vs-food choice in rhesus monkeys

Banks

Hutsell

Negus

2019

Preprint

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“…We previously suggested that, in contrast to cocaine, heroin exerts orexigenic effects and that these effects would enhance, rather than suppress, responding for the alternative nondrug reward, when choosing under the influence is permitted (Vandaele et al 2016). However, recent findings suggest that the processes controlling drugvs-food choice under opioid influence cannot be limited to the drug orexigenic effects (Chow and Beckmann 2021;Townsend et al 2021) indicating that, in agreement with the present study, the mechanisms controlling choice under drug influence are more complex than previously suggested.…”

Section: Discussionsupporting

confidence: 90%

“…Furthermore, cocaine-induced shift in preference is associated with a suppression of the activity of saccharin-coding neurons in the orbitofrontal cortex and no facilitation of the activity of cocaine-coding neurons (Guillem and Ahmed 2018). Finally, drug-induced shift in preference is not observed with heroin intoxication which is known to enhance rather than suppress eating and drinking behaviors (Cooper et al 1985;Parker et al 1992;Vandaele et al 2016; but see Chow and Beckmann 2021;Townsend et al 2021). Thus, the comparison of cocaine and heroin in a free-operant choice schedule or following pre-trial drug injections suggests that their opposite effect on preference is likely mediated by their opposite effects (suppressing versus enhancing) on the alternative nondrug reward rather than by their common priming effects on drug seeking, as seen in other behavioral paradigms (Ahmed and Cador 2006;de Wit and Stewart 1983).…”

Section: Introductionmentioning

confidence: 98%

Choosing between cocaine and sucrose under the influence: testing the effect of cocaine tolerance

Vandaele¹,

Ahmed

2021

Psychopharmacology

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Cocaine use not only depends on the reinforcing properties of the drug, but also on its pharmacological effects on alternative nondrug activities. In animal models investigating choice between cocaine and alternative sweet rewards, the latter influence can have a dramatic impact on choice outcomes. When choosing under cocaine influence is prevented by imposing sufficiently long intervals between choice trials, animals typically prefer the sweet reward. However, when choosing under the drug influence is permitted, animals shift their preference in favor of cocaine.We previously hypothesized that this preference shift is mainly due to a direct suppression of responding for sweet reward by cocaine pharmacological effects. Here we tested this hypothesis by making rats tolerant to this drug-induced behavioral suppression.Contrary to our expectation, tolerance did not prevent rats from shifting their preference to cocaine when choosing under the influence.Thus, other mechanisms must be invoked to explain the influence of cocaine intoxication on choice outcomes.

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“…For Experiment 3, we anaesthetised rats with 2%–3% isoflurane in oxygen and implanted them with polyurethane catheters into the right jugular vein using methods previously described (Townsend et al, 2021). We injected the rats with ketoprofen (5 mg·kg −1 , s.c.) immediately after the surgery and then 24 h later.…”

Section: Methodsmentioning

confidence: 99%

Sex differences in the effect of chronic delivery of the buprenorphine analogue BU08028 on heroin relapse and choice in a rat model of opioid maintenance

Bossert

Townsend

Altidor

et al. 2021

British J Pharmacology

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Background and Purpose Maintenance treatment with opioid agonists (buprenorphine, methadone) decreases opioid use and relapse. We recently modelled maintenance treatment in rats and found that chronic delivery of buprenorphine or the μ opioid receptor partial agonist TRV130 decreased relapse to oxycodone seeking and taking. Here, we tested the buprenorphine analogue BU08028 on different heroin relapse‐related measures and heroin versus food choice. Experimental Approach For relapse assessment, we trained male and female rats to self‐administer heroin (6 h·day−1, 14 days) in Context A and then implanted osmotic minipumps containing BU08028 (0, 0.03 or 0.1 mg·kg−1·d−1). Effects of chronic BU08028 delivery were tested on (1) incubation of heroin‐seeking in a non‐drug Context B, (2) extinction responding reinforced by heroin‐associated discrete cues in Context B, (3) reinstatement of heroin‐seeking induced by re‐exposure to Context A and (4) re‐acquisition of heroin self‐administration in Context A. For choice assessment, we tested the effect of chronic BU08028 delivery on heroin versus food choice. Key Results Chronic BU08028 delivery decreased incubation of heroin seeking. Unexpectedly, BU08028 increased re‐acquisition of heroin self‐administration selectively in females. Chronic BU08028 had minimal effects on context‐induced reinstatement and heroin versus food choice in both sexes. Finally, exploratory post hoc analyses suggest that BU08028 decreased extinction responding selectively in males. Conclusions and Implications Chronic BU08028 delivery had both beneficial and detrimental, sex‐dependent, effects on different triggers of heroin relapse and minimal effects on heroin choice in both sexes. Results suggest that BU08028 would not be an effective opioid maintenance treatment in humans.

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A drug-vs-food “choice” self-administration procedure in rats to investigate pharmacological and environmental mechanisms of substance use disorders

Cited by 37 publications

References 74 publications

Contextual extinction of drug-associated discriminative stimuli fails to attenuate drug-vs-food choice in rhesus monkeys

Contextual extinction of drug-associated discriminative stimuli fails to attenuate drug-vs-food choice in rhesus monkeys

Choosing between cocaine and sucrose under the influence: testing the effect of cocaine tolerance

Sex differences in the effect of chronic delivery of the buprenorphine analogue BU08028 on heroin relapse and choice in a rat model of opioid maintenance

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