@entity1024 antagonists and WIN 55212-2 [4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1-i,j]quinolin-6-one], a cannabinoid agonist, interact to produce XXXX .

@entity1024 @entity2227 @entity54271 @entity14031 @entity10024 @entity8364 @entity143 @entity35 @entity2332
CB(1) cannabinoid receptors mediate profound @entity2332 when cannabinoid agonists are administered to @entity35 . @entity2227 , the principal excitatory neurotransmitter in the central nervous system (CNS), is thought to tonically increase body temperature by activating @entity1024 ( @entity143 ) receptors. Because @entity143 antagonists block cannabinoid-induced antinociception and @entity8364 , intimate glutamatergic-cannabinoid interactions may exist in the CNS. The present study investigated the effect of two @entity143 antagonists on the hypothermic response to WIN 55212-2 [4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1-i,j]quinolin-6-one], a selective cannabinoid agonist, in @entity35 . @entity10024 -2 (1-10 mg/kg i.m.) produced dose-dependent @entity2332 that peaked 60 to 180 min postinjection. @entity14031 (5-75 mg/kg i.m.), a noncompetitive @entity143 antagonist, or @entity54271 [(-)-6-[phosphonomethyl-1,2,3,4,4a,5,6,7,8,8a-decahydro-isoquinoline-2-carboxylate]](1-4 mg/kg i.m.), a competitive and highly selective @entity143 antagonist, evoked @entity2332 in a dose-sensitive manner, suggesting that endogenous @entity2227 exerts a hyperthermic tone on body temperature. A dose of @entity14031 (10 mg/kg) that did not affect body temperature by itself potentiated the hypothermic response to @entity10024 -2 (1, 2.5, or 5 mg/kg). The enhancement was strongly synergistic, indicated by a 2.7-fold increase in the relative potency of @entity10024 -2. Similarly, a dose of @entity54271 (1 mg/kg) that did not affect body temperature augmented the @entity2332 associated with a single dose of @entity10024 (2.5 mg/kg), thus confirming that @entity143 receptors mediated the synergy. We have demonstrated previously that CB(1) receptors mediate @entity10024 -2-evoked @entity2332 in @entity35 . The present data are the first evidence that @entity143 antagonists exert a potentiating effect on cannabinoid-induced @entity2332 . Taken together, these data suggest that interactions between @entity143 and CB(1) receptors produce @entity2332 .
