Abstract:
: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 (alpha1-ARs) can facilitate cocaine-stimulated locomotion. Of the three alpha1-AR subtypes (alpha(1A), alpha(1B), and alpha(1D)) identified to date, inactivation of the alpha(1B)-AR subtype diminishes cocaine-stimulated locomotion, whereas the impact of inactivation of the alpha(1A)-AR subtype on either eating or locomotion is unknown. In the present study, we assessed the relative impact of ICV administration of the alpha(1B)-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 alpha1-AR agonists (e.g. phenylpropanolamine) to suppress eating may be related to activation of the alpha(1A)-AR subtype, whereas cocaine does not act through the alpha(1A)-AR subtype to suppress eating nor does this subtype modulate cocaine-induced hyperlocomotion.
journal_name
Life Scijournal_title
Life sciencesauthors
Clifford PS,Davis KW,Elliott AE,Wellman PJdoi
10.1016/j.lfs.2007.08.004subject
Has Abstractpub_date
2007-09-08 00:00:00pages
1059-65issue
13eissn
0024-3205issn
1879-0631pii
S0024-3205(07)00582-6journal_volume
81pub_type
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