Rewarding and locomotor-activating effects of direct dopamine receptor agonists are augmented by chronic food restriction in rats

Rationale: Previous studies indicate that chronic food restriction augments the rewarding and motor-activating effects of diverse drugs of abuse. The drugs that have so far proved susceptible to the augmenting effect of food restriction all increase synaptic concentrations of dopamine (DA). It is no t known whether behavioral effects of selective, direct DA receptor agonist s are also subject to the augmenting effect of food restriction. Objectives : The first objective of this study was to investigate whether the rewardin g and locomotor-activating effects of the D-1 agonist, A77636, and the D-2 agonist, quinpirole are augmented by chronic food restriction. The second p urpose was to investigate whether the augmented rewarding and locomotor-act ivating effects of d-amphetamine in food-restricted rats are reversed by th e D-1 antagonist, SCH23390. Methods: Rewarding effects of drugs were measur ed in terms of their ability to lower the threshold for lateral hypothalami c self-stimulation (LHSS) using a rate-frequency method. Locomotor-activati ng effects were measured in terms of the number of midline crossings exhibi ted by rats in a shuttle apparatus. Results: A77636 (1.0 and 2.5 mg/kg, i.p .) produced a greater threshold-lowering effect in food-restricted than ad libitum fed rats but produced variable effects on locomotor activity with n o difference between groups. Quinpirole (0.2 and 0.5 mg/kg, i.p.) produced a marginally greater threshold-lowering effect in food-restricted rats and a dramatic locomotor response that was exclusive to food-restricted rats. T he D, antagonist, SCH23390, at a dose of 0.01 mg/kg (i.p.), had no effect o n the lowering of LHSS threshold by amphetamine (0.5 mg/kg, i.p.) in ad lib itum fed rats but blocked the augmentation otherwise observed in food-restr icted rats. SCH23390, at a dose of 0.025 mg/kg, had no effect on locomotor activity induced by amphetamine (0.5 mg/kg) in ad libitum fed rats but bloc ked the augmentation otherwise observed in food-restricted rats. Conclusion s: These results indicate that the augmentation of reward by food restricti on extends to drugs that bypass the DA terminal and act postsynaptically. W hen taken together with prior immunohistochemical and behavioral findings, these results suggest that food restriction may increase the "enabling" eff ect of the D-1 receptor on DA-mediated behaviors.