a-procedure-to-study-effect-prolonged-food-restriction-on-heroin

A Procedure to Study the Effect of Prolonged Food Restriction on Heroin Seeking in Abstinent Rats

In human drug addicts, exposure to drug-associated cues or environments that were previously associated with drug taking can trigger relapse during ...

Concordia University

Previous research with an animal model of relapse has shown that acute food deprivation will reinstate extinguished drug seeking. Recent evidence with humans, however, suggests that chronic food restriction rather than acute food deprivation is related to increases in drug taking and relapse, emphasizing a need for an animal model to elucidate the neural mechanisms mediating the effects of chronic food restriction on drug seeking. Here we studied the effects of chronic food restriction during a period of abstinence on heroin seeking in rats.

The effects of chronic food restriction on cue-induced heroin seeking in abstinent male rats.

Drug addiction is a chronic disease characterized by recurring episodes of abstinence and relapse. The precise mechanisms underlying this pattern are yet to be elucidated, but stress is thought to be a major factor in relapse. Recently, we reported that rats under withdrawal and exposed to a mild chronic stressor, prolonged food restriction, show increased heroin seeking compared to sated controls. Previous studies demonstrated a critical role for corticotropin-releasing factor (CRF) and corticosterone, hormones involved in the stress response, in acute food deprivation-induced reinstatement of extinguished drug seeking. However, the role of CRF and corticosterone in chronic food restriction-induced augmentation of drug seeking remains unknown. Here, male Long-Evans rats were trained to self-administer heroin for 10 days in operant conditioning chambers. Rats were then removed from the training chambers, and subjected to 14 days of unrestricted (sated rats) or a mildly restricted (FDR rats) access to food, which maintained their body weight (BW) at 90% of their baseline weight. On day 14, different groups of rats were administered a selective CRF1 receptor antagonist (R121919; 0.0, 20.0 mg/kg; s.c.), a non-selective CRF receptor antagonist (α-helical CRF; 0.0, 10.0, 25.0 μg/rat; i.c.v.) or a glucocorticoid receptor antagonist (RU486; 0.0, 30.0 mg/kg; i.p.), and underwent a 1 h drug seeking test under extinction conditions. An additional group of rats was tested following adrenalectomy. All FDR rats showed a statistically significant increase in heroin seeking compared to the sated rats. No statistically significant effects for treatment with α-helical CRF, R121919, RU486 or adrenalectomy were observed. These findings suggest that stress may not be a critical factor in the augmentation of heroin seeking in food-restricted rats.

Tracey D'Cunha

Department of Psychology,
Center for Studies in Behavioural Neurobiology/Groupe de Recherche en Neurobiologie Comportementale,
Department of Psychology, Center for Studies in Behavioural Neurobiology/Groupe de Recherche en Neurobiologie Comportementale

Concordia University

A Procedure to Study the Effect of Prolonged Food Restriction on Heroin Seeking in Abstinent Rats