Rationale
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.
Materials and 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.
Keywords Activation - Glutamate receptor - Motor activity - Adaptation - Addiction - Alcohol - Excitatory amino acid - Psychostimulant - Drug abuse - Reverse tolerance