Disruption of operant oral self-administration of ethanol, sucrose, and saccharin by the AMPA/kainate antagonist, NBQX, but not the AMPA antagonist, GYKI 52466.
BACKGROUND
AMPAergic transmission has been suggested to be important in mediating the rewarding effects of drugs. We therefore examined the role of non-NMDA glutamate-receptors in mediating the reinforcing properties of ethanol in an oral self-administration paradigm.


METHODS
The competitive antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline) and the non-competitive antagonist, GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylene-dioxy-5H2,3- be nzodiazepine), were administered to animals previously trained to self-administer ethanol, sucrose, or saccharin, on a progressive ratio schedule.


RESULTS
GYKI 52466 (5 & 10 mg/kg) had no effect on operant responding for ethanol, but increased spontaneous locomotor activity, whereas the highest doses of NBQX (3 & 6 mg/kg) significantly decreased operant responding and correspondingly decreased the breaking point in responding for ethanol on a progressive ratio schedule. NBQX (but not GYKI 52466) also significantly decreased operant responding for a food reinforcer (sucrose) as well as for a sweet tasting reinforcer (saccharin). Doses of NBQX that disrupted operant performance caused a significant reduction in locomotor activity, indicating that NBQX decreased ethanol self-administration only at doses which disrupt motor activity.


CONCLUSIONS
These results suggest non-NMDA glutamate-receptors may not have a specific role in the maintenance of responding for an ethanol reinforcer, but may generally disrupt operant performance. Because, unlike GYKI 52466, NBQX possesses an action at central kainate receptors, these results suggest that kainate, but not AMPA (alpha-amino 3-hydroxy-5-methyl-4-isoxazole propionate) receptors may be important in mediating the reinforcing effects of ethanol.
Stephens
D N
DN
Laboratory of Experimental Psychology, University of Sussex, Falmer, Brighton, United Kingdom. dns@biols.susx.ac.uk
Brown
G
G
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D012439:Saccharin / Q000008:administration & dosage; D012646:Self Administration / Q000523:psychology; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage
D014151:Anti-Anxiety Agents; D002492:Central Nervous System Depressants; D011810:Quinoxalines; D018091:Receptors, AMPA; D013549:Sweetening Agents; C061950:GYKI 52466; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001569:Benzodiazepines; D000431:Ethanol; D013395:Sucrose; D012439:Saccharin