Enhanced locomotor stimulation by NMDA receptor antagonists in alcohol-sensitive ANT rats.
The ability of the antagonists for the N-methyl-D-aspartate (NMDA) type of glutamate receptor to modulate locomotor activity were compared in alcohol-sensitive (or alcohol-nontolerant, ANT) and alcohol-insensitive (or alcohol-tolerant, AT) rat lines. Both rat lines showed altered locomotor activity after acute injections of a competitive antagonist (LY235959), a glycine-site antagonist (L-701,324), or noncompetitive antagonists [MK-801, phencyclidine (PCP), and ketamine] of the NMDA receptor. MK-801 at 0.5 mg/kg caused a strong increase in horizontal activity in both rat lines, the effect being significantly greater in the ANT rats. There was a subpopulation among AT rats that was almost completely unresponsive to MK-801. This insensitivity to MK-801 correlated with the lack of c-fos induction in the retrosplenial and cingulate cortices. Fos immunoreactive cells in these brain regions after MK-801 treatment were more numerous in ANT than AT rats, although c-fos induction in the inferior olivary nucleus was similar in all animals after MK-801. The ANT rats showed greater locomotor stimulation also after ketamine and LY235959, while stimulation induced by PCP and depression induced by L-701,324 did not differ between the rat lines. The data suggest that altered NMDA receptor-mediated processes may correlate with differences in innate alcohol sensitivity in the ANT/AT rat model.
Vekovischeva
O Y
OY
Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland.
Haapalinna
A
A
Näkki
R
R
Sarviharju
M
M
Honkanen
A
A
Heikkilä
J
J
Korpi
E R
ER
D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D013045:Species Specificity
D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; C088643:LY 235959