Behavioral sensitization to ethanol does not result in cross-sensitization to NMDA receptor antagonists.
BACKGROUND
Behavioral sensitization to the locomotor stimulant effects of ethanol may be related to neuroadaptations within glutamatergic systems. Previous research has suggested that the N-methyl-D: -aspartate (NMDA) subclass of glutamate receptors is critical for the development of ethanol sensitization. We hypothesized that sensitization to ethanol would be associated with changes in sensitivity to NMDA receptor ligands.


METHODS
DBA/2J and heterogeneous stock (HS) mice were injected with ethanol or saline for 12 days and tested for their acute and sensitized responses to the locomotor effects of ethanol in automated activity monitors. After this treatment phase, mice were challenged with MK-801, ethanol, or ketamine, and locomotor activity was measured for 20 to 60 min. Other ethanol-sensitized and nonsensitized mice were assessed for sensitivity to the effects of NMDA after tail-vein infusions.


RESULTS
There was no evidence for cross-sensitization to MK-801 or ketamine, or altered sensitivity to NMDA in ethanol-sensitized animals, in any experiment. In one experiment, previously ethanol-treated HS mice developed tolerance to the locomotor stimulant effects of ketamine.


CONCLUSIONS
These results indicate that ethanol-induced behavioral sensitization is not associated with increased behavioral sensitivity to NMDA receptor antagonists or altered sensitivity to NMDA receptor agonists. To the extent that changes in sensitivity to these ligands reflect changes in NMDA receptors, these results are inconsistent with the hypothesis that ethanol sensitization is associated with alterations in NMDA receptor-mediated processes.
Meyer
Paul J
PJ
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
Phillips
Tamara J
TJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006967:Hypersensitivity / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012684:Sensory Thresholds / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors
D002492:Central Nervous System Depressants; D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D016202:N-Methylaspartate; D007649:Ketamine; D016291:Dizocilpine Maleate