Escalation of food-maintained responding and sensitivity to the locomotor stimulant effects of cocaine in mice

Abstract

Escalation of drug self-administration is a consequence of extended drug access and is thought to be specifically related to addiction, but few studies have investigated whether intake of non-drug reinforcers may also escalate with extended-access. The goal of these studies was to determine the effects of limited and extended-access to food reinforcers on behavioral and pharmacological endpoints in mice. In distinct groups, responding on a lever was maintained by liquid reinforcement, or nose-poke responses were maintained by sucrose pellets or liquid food in sessions lasting 1 hour (limited-access) or 10 hours (extended-access). The reinforcing strength of each food, as well as reinforcer-associated cues, was tested before and after extended-access using a progressive ratio (PR) schedule, and locomotor activity in response to novelty and increasing doses of cocaine was assessed in an open field setting in all animals after access to food reinforcers. Escalation of lever-pressing behavior reinforced by liquid food, but not nose-poke behavior reinforced by liquid food or sucrose pellets, was observed across successive extended-access sessions. A concomitant increase in the reinforcing strength of liquid food and its associated cues was apparent in mice that escalated their responding, but not in mice that did not escalate. Finally, extended reinforcer access leading to behavioral escalation was accompanied by an increased sensitivity to the psychostimulant effects of cocaine compared to limited-access. These findings indicate that behavioral escalation can develop as a consequence of extended-access to a non-drug reinforcer, although both the nature of the reinforcer (liquid versus solid food) and the topography of the operant response (lever versus nose-poke) modulate its development. These data also suggest that some of the behavioral and pharmacological corrolaries of behavioral escalation observed following extended-access to drug self-administration may not be due to drug exposure, but rather, may result from basic behavioral processes which underlie operant responding maintained by appetitive stimuli.

The effects of response operandum and prior food training on intravenous nicotine self-administration in rats

“…Consistent with previous research using non-nicotine reinforcers (Caine et al 1999;David et al 2001;Deiana et al 2007;Goeders et al 2009), the use of NP rather than LVR apparatus facilitated the spontaneous acquisition of nicotine IVSA. However, in contrast to these past studies, the difference in levels of responding during acquisition persisted throughout training, across various doses of nicotine and influenced reinstatement of nicotine-seeking behavior.…”

Less is more: prolonged intermittent access cocaine self-administration produces incentive-sensitization and addiction-like behavior

“…Total cocaine consumption produced by the IntA procedure used here is comparable to that seen under ShA conditions, and is far less than with LgA (Zimmer et al, 2012; Calipari et al, 2013; see Table 1). Indeed, it has been suggested previously that the high level of consumption produced by LgA is not required to produce escalation (Beckmann et al , 2012; Goeders et al , 2009; Mandt et al , 2012). It is worth noting that Zimmer et al (2012) did not explicitly report escalation in their IntA groups.…”

Escalation in high fat intake in a binge eating model differentially engages dopamine neurons of the ventral tegmental area and requires ghrelin signaling

“…Intake escalation is a relevant feature of these binge eating models because it is associated to the feeling of loss of control over eating, which is a typical characteristic of human binge eating episodes (Goeders et al, 2009;Perello et al, 2014). Of course, human binge eating episodes are a much more complex behavior affecting people for long periods of time (Wolfe et al, 2009).…”

“…Of course, human binge eating episodes are a much more complex behavior affecting people for long periods of time (Wolfe et al, 2009). Still, the study of rodent models in a short term fashion can be useful to get insights into some of the neuronal circuits recruited under particular conditions, as it has been previously done in the drugs of abuse research field (Goeders et al, 2009;Steketee and Kalivas, 2011). Some of the proposed mechanisms mediating intake escalation during the successive exposures to drugs of abuse include tolerance, behavioral sensitization or habit formation, and the mesolimbic dopamine pathway have been suggested as a potential target underlying these behavioral changes (Berridge, 2007;Steketee and Kalivas, 2011).…”

“…Interestingly, several studies using intermittent or daily access to palatable foods have shown that rodents' consumption gradually escalates over the initial accesses until it finally stabilizes Bake et al, 2014;Berner et al, 2008;Davis et al, 2007;Lardeux et al, 2013;Rada et al, 2005;Wojnicki et al, 2008). Intake escalation appears to be a critical phenomenon since it has been proposed to mediate the transition from a controlled to a compulsive or loss of control behavior (Goeders et al, 2009). Notably, intake escalation is also observed with drugs of abuse, including cocaine, heroin and amphetamine, among others (Zernig et al, 2007).…”