Effects of ICV administration of the alpha1A-adrenoceptor antagonist 5-methylurapidil on concurrent measures of eating and locomotion after cocaine in the rat

Psychostimulants including amphetamine and cocaine induce locomotion and stereotypy and suppress eating. Although the capacity of cocaine to alter locomotion is usually viewed as related to dopamine neurotransmission, recent studies suggest that norepinephrine, acting through alpha1-adrenergic receptors (α1-ARs) can facilitate cocaine-stimulated locomotion. Of the three α1-AR subtypes (α1A, α1B, and α1D) identified to date, inactivation of the α1B-AR subtype diminishes cocaine-stimulated locomotion, whereas the impact of inactivation of the α1A-AR subtype on either eating or locomotion is unknown. In the present study, we assessed the relative impact of ICV administration of the α1B-AR antagonist 5-methylurapidil (5-MU) on cocaine-stimulated hyperlocomotion and hypophagia, using a concurrent method [Wellman, P.J., Ho, D.H., Davis, K.W., 2005. Concurrent measures of feeding and locomotion in rats. Physiology of Behavior 84 (5), 769–774.]. Rats were infused ICV with one of 3 doses of 5-MU (0, 3, or 30 nmol) and then injected (i.p.) with 0, 2.5, 5.0, 10.0, or 20.0 mg/kg cocaine HCl on each of five tests. Rats always received the same 5-MU dose, but a different cocaine dose on each trial. Feeding and locomotion were assessed concurrently during a 45-min postinjection period. Significant suppression of eating was noted at 2.5 mg/kg cocaine, a dose that does not alter forward locomotion in the rat. Administration of 5-MU did not alter locomotion in rats treated with saline, but did significantly increase baseline food intake. Neither cocaine-induced hypophagia nor hyperlocomotion was altered by ICV administration of 5-MU. These results suggest that the capacity of α1-AR agonists (e.g. phenylpropanolamine) to suppress eating may be related to activation of the α1A-AR subtype, whereas cocaine does not act through the α1A-AR subtype to suppress eating nor does this subtype modulate cocaine-induced hyperlocomotion.