Antagonism of neuropeptide YY1 receptors does not inhibit ethanol's effects on cortical EEG and ERPs in Wistar rats.
OBJECTIVE
Ethanol and neuropeptide Y (NPY) can have additive neurobehavioral effects. In the present study, the NPY Y1 receptor antagonist BIBP3226 was administered alone or in combination with a moderate dose of ethanol to determine whether it interacted with the neurobehavioral effects of ethanol.


METHODS
Male Wistar rats were implanted with cortical recording electrodes and a lateral ventricular cannula. The effects of 1 nmol BIBP3226, 0.75 g/kg ethanol and the combination (BIBP3226 + EtOH) on neurophysiological activity and locomotion were then assessed.


RESULTS
Ethanol significantly increased 1-2 Hz parietal cortical power and this effect was partially antagonized by BIBP3226. Peak frequencies in the parietal cortical 6-8 Hz and 8-16 Hz bands were also altered by ethanol, but these effects were not reversed by BIBP3226. BIBP3226 or ethanol, when administered alone, did not alter motor activity or cortical event-related potentials (ERPs) but administration of BIBP3226 + EtOH reduced motor activity, reduced parietal cortical N1 ERP amplitude and increased frontal cortical N1 ERP latency.


CONCLUSIONS
In the present study, the most prominent effect of antagonizing central NPY Y1 receptors was a facilitation of the effects of ethanol. In particular, the effects of combined administration of BIBP3226 and ethanol are indicative of enhanced sedation and possibly cognitive impairment.
Slawecki
Craig J
CJ
The Scripps Research Institute, Department of Neuropharmacology, CFN-14, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. cslawecki@scripps.edu
Thorsell
Annika
A
Ehlers
C L
CL
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D005071:Evoked Potentials / Q000502:physiology*; D005625:Frontal Lobe / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D010296:Parietal Lobe / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*
C092926:BIBP 3226; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D000431:Ethanol; D001120:Arginine