The non-competitive NMDA receptor antagonist (+)MK-801 counteracts the long-lasting attenuation of the hypothermic response induced by acute doses of 8-OH-DPAT in the rat.
The effects of acute doses of 8-hydroxy 2-(di-n-dipropylamino)tetralin (8-OH-DPAT) on the hypothermic response, induced by a challenge dose of 8-OH-DPAT, were examined in rats. Acute doses of 8-OH-DPAT (1.0 or 0.5 mg/kg, s.c.) significantly attenuated the hypothermic response induced by 8-OH-DPAT (0.05 mg/kg, s.c.). The response to 8-OH-DPAT was almost abolished between 4 hr and 4 days and the attenuation of the response lasted for 21 days. On day 28 the response had returned to the control level. The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo-(a,d)cyclohepten-5,10-imine [(+)MK-801], blocked this long-lasting attenuation of the 8-OH-DPAT-induced hypothermic response. Given on its own, (+)MK-801 did not reduce body temperature, at the doses used in the experiments but the drug did block the acute effects of 8-OH-DPAT, at the same doses which blocked the attenuation of the hypothermic response. The present data suggest that stimulation of glutamate NMDA receptors may underlie the long-lasting effect of acute injections of 8-OH-DPAT.
Rényi
L
L
Department of Behavioural Pharmacology, Astra Arcus AB, Södertälje, Sweden.
Möller
K A
KA
Ensler
K
K
Evenden
J
J
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin