The behavioural effects of an N-methylaspartate receptor antagonist following application to the lumbar spinal cord of conscious rats.
The selective N-methylaspartate (NMA) receptor antagonist 2-amino-5-phosphonopentanoate (AP5) has been applied to the lumbar region of the spinal cord in conscious rats through chronically implanted intrathecal cannulae. Administration of AP5 was compared with administration of 2-amino-4-phosphonobutyrate (AP4), morphine and control injections. Intrathecal injection of AP5 (250 nmol) produced extensor paralysis in the hindquarters and depression of aversive responses to tail heat (54 degrees C), paw heat (hotplate 56.5 degrees C) and paw pressure. Depression of AP5 of the vocal response to aversive electrical stimuli, applied to the tail, suggested that AP5 produced analgesia independently of locomotor paralysis. Intrathecal injection of morphine (20-30 nmol) produced no observed locomotor effects, but depressed responses to all the aversive stimuli. Intrathecal injection of AP4 had no significant effects. When tritiated AP5 was administered intrathecally, the proportion of radioactivity recovered from the lumbar spinal cord suggested that the concentration of AP5, which produced locomotor depression and analgesia, was likely to have been in the range (15-75 microM) known to depress excitatory transmission in isolated spinal cord preparations. It is concluded that synaptic activation of n-methylaspartate receptors is important in spinal pathways which control locomotion, posture and central transmission of nociceptive information.
D015763:2-Amino-5-phosphonovalerate; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D005971:Glutamates / Q000494:pharmacology; D005973:Glutamine / Q000031:analogs & derivatives*; D006614:Hindlimb / Q000294:innervation; D007278:Injections, Spinal; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000294:innervation*; D009619:Nociceptors / Q000187:drug effects*; D010875:Pipecolic Acids / Q000494:pharmacology; D011187:Posture; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate; D013116:Spinal Cord / Q000187:drug effects*; D013623:Tail / Q000294:innervation; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000613:Aminobutyrates; D005971:Glutamates; D010875:Pipecolic Acids; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D005973:Glutamine; C029262:2,3-piperidinedicarboxylic acid; D015763:2-Amino-5-phosphonovalerate; D009020:Morphine; C042626:gamma-glutamylaminomethylsulfonic acid; C012729:2-amino-4-phosphonobutyric acid; D014633:Valine