Relative reinforcing effects of cocaine and 3,4-methylenedioxypyrovalerone (MDPV) under a concurrent access self-administration procedure in rats

Seaman, Robert; Rice, Kenner C.; Collins, Gregory T.

doi:10.1016/j.drugalcdep.2022.109299

Cited by 8 publications

(10 citation statements)

References 33 publications

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“…Some rats alternated exclusive responding for either methamphetamine or fentanyl across days, whereas the remaining rats maintained concurrent methamphetamine and fentanyl intake within each session. The prevalence of rats responding for both methamphetamine and fentanyl in the current studies is in stark contrast to what was observed when rats are provided concurrent access to two drugs from the same class, MDPV and cocaine ( 37 ). In those studies, MDPV and cocaine acted as economic substitutes with nearly exclusive choice occurring in all subjects and determined by the relative cost of each drug.…”

Section: Discussioncontrasting

confidence: 83%

“…In the current studies, when rats were provided concurrent access to varying intravenous doses of methamphetamine and fentanyl (i.e., the cost of each drug was manipulated in the presence of the training dose of the alternative), more responding was allocated toward the cheaper alternative, however, responding tended not to be exclusive, suggesting that stimulants and opioids appear to function as imperfect substitutes. This is in contrast to the largely exclusive choice that was observed when two drugs of the same class, MDPV and cocaine, were concurrently available ( 37 ) and suggests that although cost might largely dictate choice of methamphetamine or fentanyl, there are other contributors to drug choice when a stimulant and opioid are concurrently available (e.g., a possible synergistic interaction between the two drugs). One consideration regarding the interpretation of these data is that for this initial study, varying doses of each drug were evaluated only when the training dose of the other drug was concurrently available.…”

Section: Discussionmentioning

confidence: 78%

“…Rats were anesthetized with 2–3% isoflurane and prepared with chronic indwelling catheters in the left and right femoral veins using procedures similar to those described previously ( 37 , 47 , 48 ). Catheters were tunneled under the skin and attached to a vascular access button placed in the mid-scapular region.…”

Section: Methodsmentioning

confidence: 99%

“…Extinction conditions remained in place for at least 7 sessions, and until the total number of lever responses on both levers was ≤ 15% of baseline responding. Once extinction criteria were met, a series of 4 reinstatement tests were performed as described previously ( 37 , 44 ). Briefly, reinstatement tests were identical to self-administration conditions with the exceptions that: ( 1 ) intravenous pretreatments of saline (cue-induced reinstatement) or drug (cue + drug-primed reinstatement) were administered 5 min before the session; ( 2 ) sample trials were omitted from the session; and ( 3 ) completion of response requirements resulted in the delivery of a saline infusion in conjunction with the methamphetamine- or fentanyl-associated stimuli.…”

Section: Methodsmentioning

confidence: 99%

“…As the cost of one drug is increased, intake of the fixed cost alternative drug may increase (substitutes), decrease (complements), or stay the same (independents). Previous work from our laboratory used a concurrent access procedure in rats to characterize interactions between the reinforcing effects of two stimulant drugs, 3,4-methylenedioxypyrovalerone (MDPV) and cocaine ( 37 ). When functionally equivalent doses of MDPV and cocaine (as determined by a progressive ratio schedule of reinforcement) were made concurrently available, responding tended to be allocated toward one lever or the other, with the behavior of a subset of rats maintained almost exclusively by MDPV, whereas for the remaining rats behavior was maintained almost exclusively by cocaine.…”

Section: Introductionmentioning

confidence: 99%

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Modeling Stimulant and Opioid Co-use in Rats Provided Concurrent Access to Methamphetamine and Fentanyl

2022

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Concurrent use of stimulants (e.g., methamphetamine) and opioids (e.g., fentanyl) has become increasingly common in recent years and continues to pose an enormous health burden, worldwide. Despite the prevalence, relatively little is known about interactions between the reinforcing effects of stimulants and opioids in this pattern of polysubstance use. The goals of the current study were to evaluate the relative reinforcing and relapse-related effects of methamphetamine and fentanyl using a concurrent access, drug-vs.-drug choice procedure. Male Sprague-Dawley rats were first allowed to acquire self-administration for either 0.1 mg/kg/infusion methamphetamine or 0.0032 mg/kg/infusion fentanyl, independently, after which concurrent access to both drugs was provided. When training doses of methamphetamine and fentanyl were concurrently available, a subset of rats self-administered both drugs, either within a session or alternating across sessions, whereas the remaining rats responded exclusively for one drug. When the cost of the preferred drug was increased (i.e., unit dose reduced), or the cost of the non-preferred drug was decreased (i.e., unit dose increased), choice was largely allocated toward the cheaper alternative. Following extinction of responding, methamphetamine- and fentanyl-paired cues reinstated responding on both levers. Responding reinstated by a priming injection of methamphetamine or fentanyl allocated more responding to the lever previously reinforced by the priming drug. The current studies suggest that choice of methamphetamine and fentanyl is largely allocated to the cheaper alternative, although more co-use was observed than would be expected for economic substitutes. Moreover, they lay the groundwork for more fully evaluating interactions between commonly co-abused drugs (e.g., stimulants and opioids) in order to better understand the determinants of polysubstance use and develop effective treatment strategies for individuals suffering from a polysubstance use disorder.

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Section: Discussioncontrasting

confidence: 83%

Section: Discussionmentioning

confidence: 78%