Food restriction increases acquisition, persistence and drug prime-induced expression of a cocaine-conditioned place preference in rats

Abstract

Cocaine conditioned place preference (CPP) is more persistent in food-restricted than ad libitum fed rats. This study assessed whether food restriction acts during conditioning and/or expression to increase persistence. In Experiment 1, rats were food-restricted during conditioning with a 7.0 mg/kg (i.p.) dose of cocaine. After the first CPP test, half of the rats were switched to ad libitum feeding for three weeks, half remained on food restriction, and this was followed by CPP testing. Rats tested under the ad libitum feeding condition displayed extinction by the fifth test. Their CPP did not reinstate in response to overnight food deprivation or a cocaine prime. Rats maintained on food restriction displayed a persistent CPP. In Experiment 2, rats were ad libitum fed during conditioning with the 7.0 mg/kg dose. In the first test only a trend toward CPP was displayed. Rats maintained under the ad libitum feeding condition did not display a CPP during subsequent testing and did not respond to a cocaine prime. Rats tested under food-restriction also did not display a CPP, but expressed a CPP following a cocaine prime. In Experiment 3, rats were ad libitum fed during conditioning with a 12.0 mg/kg dose. After the first test, half of the rats were switched to food restriction for three weeks. Rats that were maintained under the ad libitum condition displayed extinction by the fourth test. Their CPP was not reinstated by a cocaine prime. Rats tested under food-restriction displayed a persistent CPP. These results indicate that food restriction lowers the threshold dose for cocaine CPP and interacts with a previously acquired CPP to increase its persistence. In so far as CPP models Pavlovian conditioning that contributes to addiction, these results suggest the importance of diet and the physiology of energy balance as modulatory factors.

Caloric Restriction Enhances Fear Extinction Learning in Mice

“…Functional MRI studies using disorder-relevant stimuli such as high calorie foods and distorted body images induce elevated amygdala reactivity in subjects with AN relative to healthy controls (Ellison et al, 1998;Joos et al, 2011); positron emission tomography studies show hypoperfusion of structures associated with fear extinction-namely the medial prefrontal cortex-and hyperperfusion of the amygdala À hippocampal complex in AN (Takano et al, 2001). Consistent with this clinical perspective, our results suggest that CR may normalize dysregulated fear responses in AN, which in combination with trait or acquired alterations in cortico-striatal circuit function that have been described in AN, may help explain why dieting behavior is so vigorously reinforced as well as the high comorbidity of anorexia with obsessive-compulsive disorder (Milad and Rauch, 2012;Wagner et al, 2007;Zheng et al, 2012).…”

Nucleus accumbens AMPA receptor involvement in cocaine-conditioned place preference under different dietary conditions in rats

“…Moreover, one-third of callers to the National Cocaine Hotline who met criteria for cocaine abuse also met criteria for bulimia and/or anorexia nervosa (Jonas and Gold 1987). Using a CPP paradigm, it was previously observed that FR in rats increases the incentive effect of a cocaine-paired environment in much the same way that it increases the rewarding effect of cocaine itself (Liu et al 2011; Zheng et al 2012; Zheng et al 2013). This observation suggested that FR may not only increase vulnerability to initial drug use by enhancing reward magnitude but may increase relapse risk by enhancing the incentive effect of contexts associated with the subjective effects of cocaine.…”

“…This well-established effect is due, at least in part, to increased drug reward magnitude which has been attributed to increased D1 dopamine (DA) receptor signaling and calcium-permeable AMPA receptors (CP-AMPARs) in nucleus accumbens (NAc) shell (Cabeza de Vaca and Carr 1998; Carr et al 2003; Carr et al 2010). From a clinical standpoint, an equally if not more hazardous effect of food restriction (FR) is the enhanced behavioral responsiveness to a drug-paired context, as demonstrated in cocaine conditioned place preference (CPP) studies (Liu et al 2011; Zheng et al 2012; Zheng et al 2013). Context-induced craving is a common relapse trigger in addicts (Childress et al 1993; See 2002), and it may be presumed that the hyperphagia and body weight gain that accompany psychostimulant abstinence sometimes provoke weight loss dieting (Orsini et al 2014).…”

“…It was previously shown that cocaine CPP is more persistent in FR than ad libitum fed (AL) rats, and that persistence is dependent on FR during CPP expression testing (Liu et al 2011; Zheng et al 2012). Further, CPP magnitude and persistence did not vary according to degree of acute food deprivation or circulating levels of ghrelin, insulin, or corticosterone, suggesting involvement of stable neuroadaptations (Zheng et al 2013).…”

The Enigmatic Persistence of Anorexia Nervosa

“…Furthermore, a substantial body of work by Carr et al (49, 50) has established that weight loss enhances the rewarding effects of drugs of abuse and up-regulates mechanisms of synaptic plasticity in the nucleus accumbens. These findings suggest a mechanistic basis for the development of particularly well-entrenched habits, such as resistance of cocaine-conditioned behavior to extinction in food-restricted rodents (51). …”