Conflation of cocaine seeking and cocaine taking responses in IV self-administration experiments in rats: Methodological and interpretational considerations

Abstract

IV drug self-administration is a special case of an operant task. In most operant experiments, the instrumental response that completes the schedule requirement is separate and distinct from the consumptive response (e.g. eating or drinking) that follows the delivery of the reinforcing stimulus. In most IV self-administration studies drug seeking and drug taking responses are conflated. The instrumental lever press or nose poke is also a consumptive response. The conflation of these two response classes has important implications for interpretation of the data as they are differentially regulated by dose and price. The types of pharmacological pretreatments that affect appetitive responses are not necessarily the same as those that affect consumptive responses suggesting that the neurobiology of the two response classes are to some extent controlled by different mechanisms. This review discusses how schedules of reinforcement and behavioral economic analyses can be used to assess the regulation of drug seeking and drug taking separately. New methods are described that allow the examination of appetitive or consumptive responding in isolation and provide subjects with greater control over the self-administered dose. These procedures provide novel insights into the regulation of drug intake. Cocaine intake patterns that result in large, intermittent spikes in cocaine levels are shown to produce increases in appetitive responding (i.e. drug seeking). The mechanisms that control drug intake should be considered distinct from appetitive and motivational processes and should be taken into consideration in future IV self-administration studies.

Choice between delayed food and immediate opioids in rats: treatment effects and individual differences

“…For example, long-access sessions increase the rate of drug intake (Lenoir et al 2013), and the value of a self-administered drug can be increased by manipulating access conditions (Roberts et al 2013) or making the drug function as a negative reinforcer (through withdrawal relief; Negus 2006). Procedures such as these might increase preference for immediate drug reward over delayed nondrug reward (i.e., increase the steepness of the delay discounting curves).…”

Susceptibility to traumatic stress sensitizes the dopaminergic response to cocaine and increases motivation for cocaine

“…Specifically, physiological changes to mesolimbic dopamine (DA) neurons determine susceptibility vs resilience to stress (Friedman et al, 2014; Krishnan et al, 2007), and extensive evidence indicates that the mesolimbic DA system is critically involved in the acute reinforcing effects of cocaine (Koob and Volkow, 2010; Roberts et al, 2013). Consistent with these observations, susceptible and resilient rodents express differential conditioned place preference for cocaine (Krishnan et al, 2007), and thus it is feasible that susceptible and resilient subjects may also express differences in the dopaminergic response to cocaine.…”

The dual action of estrogen hypothesis

“…every response immediately results in cocaine being administered) can be considered as the consummatory component of drug taking behavior ([30, 31]). The acquisition of self-administration of cocaine by rats is enhanced by estradiol but requires several days of estradiol administration and experience to be acquired [32, 33].…”