MORPHINE MODULATES EXCITATORY AMINO ACID-INDUCED ACTIVITY IN THE MOUSE SPINAL-CORD - SHORT-TERM EFFECTS ON N-METHYL-D-ASPARTATE (NMDA) AND LONG-TERM EFFECTS ON KAINIC ACID
Ry. Yukhananov et Aa. Larson, MORPHINE MODULATES EXCITATORY AMINO ACID-INDUCED ACTIVITY IN THE MOUSE SPINAL-CORD - SHORT-TERM EFFECTS ON N-METHYL-D-ASPARTATE (NMDA) AND LONG-TERM EFFECTS ON KAINIC ACID, Brain research, 646(2), 1994, pp. 194-200
Excitatory amino acid (EAA) antagonists and phencyclidine (PCP) ligand
s inhibit the development of morphine tolerance and dependence. The pr
esent study tested the hypothesis that opioids increase EAA-induced ac
tivity by monitoring morphine's effect on the caudally-directed biting
and scratching behaviors produced in mice by intrathecal (i.t.) injec
tions of either N-methyl-D-aspartate (NMDA) or kainic acid (KA). A sin
gle injection of 10 mg/kg of morphine i.p. had no effect on the intens
ity of behaviors induced 2 h later by KA but inhibited NMDA-induced ac
tivity. Pretreatment with 100 mg/kg of morphine i.p. 24 h before testi
ng did not alter NMDA-induced behaviors, but attenuated sensitization
to repeated injections of KA, which is thought to reflect activation o
f primary afferent C-fibers. Coadministration of 0.1 mu g of naloxone
with EAAs did not alter responses to either NMDA or KA in control mice
, however, 2 h after 10 mg/kg of morphine, inclusion of naloxone poten
tiated NMDA-induced activity without altering responses to KA. 24 h af
ter 100 mg/kg of morphine, naloxone, coadministered with KA, was also
able to reverse the inhibitory effect of morphine pretreatment on KA-i
nduced activity. In summary, morphine produces short-term inhibitory a
nd excitatory effects on NMDA-induced activity, the latter of which is
unmasked by naloxone. Morphine has no immediate effect on KA-induced
activity but is able to bring about a long-term inhibition of sensitiz
ation to KA, an effect that is reversed by naloxone. Activity along pa
thways activated by NMDA and KA may, therefore, contribute to differen
t aspects of opioid tolerance or withdrawal.