Reinforcer-dependent enhancement of operant responding in opioid-withdrawn rats

Abstract

Rationale and objective-Opioid withdrawal increases the reinforcing effectiveness of the µ-opioid agonist remifentanil in rodents. The current study explored the selectivity of this effect by assessing operant behavior maintained by drug and non-drug reinforcers, remifentanil, cocaine, a palatable liquid food, and standard food pellets, as a function of opioid dependence and withdrawal.Materials and methods-Operant responding exhibited by nondependent, morphine-naïve groups was compared with responding exhibited by morphine-dependent and withdrawn groups. Dependence was established using a noncontingent morphine dosing procedure that has been previously verified to maintain dependence while allowing for daily behavioral observation during a withdrawn state. Behavior maintained by remifentanil (0.10-10.0 µg/kg/infusion), cocaine (0.032-1.0 mg/kg/infusion), a palatable liquid food reinforcer (3.2-100.0% Vanilla Ensure ® and water), or food pellets was assessed in dependent and nondependent groups.Results-Morphine withdrawal enhanced remifentanil self-administration, resulting in an upward and rightward shift of the descending limb of the dose-response curve, and increased operant responding for both food reinforcers. However, opioid withdrawal did not affect cocaine self-administration, nor did it affect responding for water.Conclusions-Enhanced operant responding observed under opioid-dependent and withdrawn conditions, while selective, is generalized to some nonopioid reinforcers.

Increased motivation to eat in opiate-withdrawn mice

“…However, in the latter study, operant behaviour testing is carried out ∼23 h after morphine dosing, while the rats are in a marked negative energy balance status. Indeed, unlike the control rats, the morphine-treated rats fail to gain BW throughout the study (Cooper et al 2010). This makes it difficult to dissociate the motivational from the energy-driven properties of food intake in opiate-withdrawn rats.…”

“…Unlike prior reports (Cooper et al 2010;Harris and Aston-Jones 2003), in the present study, mice are trained in a food-driven operant behaviour paradigm prior to being dosed with morphine. We find that CD-1 mice rapidly acquire a HPF-driven operant task, as indicated by the relatively elevated food-directed active nose-poke and DI (∼100%) values.…”

“…Alternatively, the food used is not able to attenuate the negative affective-like states of opiate withdrawal (see below for further discussion of the latter point). A more recent study shows that morphine withdrawal increases operant responding for standard food pellets in rats (Cooper et al 2010). However, in the latter study, operant behaviour testing is carried out ∼23 h after morphine dosing, while the rats are in a marked negative energy balance status.…”

“…Moreover, "precipitation" of opiate withdrawal by relatively small amounts of the opioid receptor antagonist naloxone suppresses fooddriven operant behavior in rats implanted with morphine pellets (Schulteis et al 1994). On the other hand, a more recent study report increased operant behavior for food in rats undergoing early (∼23-h) opiate withdrawal (Cooper et al 2010). However, in the latter study, food-driven operant behavior may be due to the remarkable energy deficiency associated with intermittent morphine dosing and early opiate withdrawal phases.…”

CRF2 Receptor Deficiency Eliminates the Long-Lasting Vulnerability of Motivational States Induced by Opiate Withdrawal

“…For instance, opiate-withdrawn rats and monkeys display increased self-administration of the potent μ-opioid receptor agonists heroin or remifentanil (Cooper et al, 2008;Gerak et al, 2009). Moreover, opiate-withdrawn rats and mice display increased operant behavior for food, suggesting profound and generalized alterations in motivational processes that may dramatically reduce the ability to overcome drug dependence (Cooper et al, 2010;Rouibi and Contarino, 2012;Steinfels and Young, 1981). More recently, CRF 2 receptor deficiency is shown to attenuate the motivational effect of initial opiate withdrawal phases (Rouibi and Contarino, 2013).…”