Kd. Carr et al., Rewarding and locomotor-activating effects of direct dopamine receptor agonists are augmented by chronic food restriction in rats, PSYCHOPHAR, 154(4), 2001, pp. 420-428
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.