TY - JOUR
T1 - 7-Nitroindazole and methylene blue, inhibitors of neuronal nitric oxide synthase and NO-stimulated guanylate cyclase, block MK-801-elicited behaviors in mice
AU - Deutsch, Stephen I.
AU - Rosse, Richard B.
AU - Paul, Steven M.
AU - Tomasino, Vincent
AU - Koetzner, Lee
AU - Morn, Cassandra B.
AU - Mastropaolo, John
PY - 1996/7
Y1 - 1996/7
N2 - We examined the abilities of 7-nitroindazole and methylene blue, inhibitors of the neuronal isoform of nitric oxide synthase (NOS) and nitric oxide-stimulated guanylate cyclase activity respectively, to attenuate explosive episodic jumping behavior(s) ('popping') elicited by MK-801 in mice. MK-801, like phencyclidine (PCP), is a high-affinity, noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. We have postulated that MK-801-elicited popping behavior in mice represents an animal model of schizophrenia, because popping behavior is markedly inhibited/antagonized by both typical and atypical antipsychotic drugs. In the present study, popping behavior induced by MK-801 was measured using an automated detection system that quantifies vertical displacements on the testing platform. 7-Nitroindazole (100 mg/kg) and methylene blue (32 and 100 mg/kg) significantly reduced the number and force of MK-801-elicited popping behavior. Mouse rotorod performance did not differ between animals receiving 7-nitroindazole, methylene blue, or their respective vehicles, suggesting that attenuation of MK-801-elicited popping behavior was not due to either sedation or ataxia caused by 7-nitroindazole or methylene blue. Our findings suggest that nitric oxide may, in part, mediate behaviors induced by NMDA receptor antagonists, like MK-801, and that inhibitors of NOS may have antipsychotic actions.
AB - We examined the abilities of 7-nitroindazole and methylene blue, inhibitors of the neuronal isoform of nitric oxide synthase (NOS) and nitric oxide-stimulated guanylate cyclase activity respectively, to attenuate explosive episodic jumping behavior(s) ('popping') elicited by MK-801 in mice. MK-801, like phencyclidine (PCP), is a high-affinity, noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. We have postulated that MK-801-elicited popping behavior in mice represents an animal model of schizophrenia, because popping behavior is markedly inhibited/antagonized by both typical and atypical antipsychotic drugs. In the present study, popping behavior induced by MK-801 was measured using an automated detection system that quantifies vertical displacements on the testing platform. 7-Nitroindazole (100 mg/kg) and methylene blue (32 and 100 mg/kg) significantly reduced the number and force of MK-801-elicited popping behavior. Mouse rotorod performance did not differ between animals receiving 7-nitroindazole, methylene blue, or their respective vehicles, suggesting that attenuation of MK-801-elicited popping behavior was not due to either sedation or ataxia caused by 7-nitroindazole or methylene blue. Our findings suggest that nitric oxide may, in part, mediate behaviors induced by NMDA receptor antagonists, like MK-801, and that inhibitors of NOS may have antipsychotic actions.
KW - 7-Nitroindazole
KW - Antipsychotic
KW - MK-801
KW - Methylene blue
KW - Phencyclidine
KW - Popping behavior
UR - http://www.scopus.com/inward/record.url?scp=0030201026&partnerID=8YFLogxK
U2 - 10.1016/0893-133X(95)00153-5
DO - 10.1016/0893-133X(95)00153-5
M3 - Article
C2 - 8797190
AN - SCOPUS:0030201026
SN - 0893-133X
VL - 15
SP - 37
EP - 43
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 1
ER -