Excitatory amino acids (EAAs) administered intrathecally (i.t.) in the mouse elicit a caudally directed biting and scratching behavior. N-methyl-d-aspartate (NMDA) is a potent agonist that produces this behavior, and its action is inhibited by the NMDA receptor antagonist, d-2-aminophosphonovaleric acid (d-APV). The behavioral response to the agonists resembles the response to i.t. substance P (SP) except that the response to the EAAs is more intense and, at higher doses, is accompanied by vocalization. The behavioral response to i.t. EAAs is not enhanced by i.t. SP. Whereas [d-Ala2-d-Leu5]enkephalin (DADL) and norepinephrine (NE) inhibit SP-induced biting and scratching, these compounds only partially inhibit EAA-induced behavior. Phencyclidine (PCP), on the other hand, inhibits completely NMDA-induced behavior but not behavior induced by SP or other EAAs. We conclude that the behavior induced by i.t. EAAs is mediated by spinal EAA receptors and that this response is pharmacologically distinct from responses to SP.
Bibliographical noteFunding Information:
We thank Drs. Stephen Crooks and Rodney Johnson (Department of Medicinal Chemistry), and Drs. Michael Robinson and James Koerner (Department of Biochemistry) for gifts of compounds and for their advice. This work was supported by NIDA Grants 01933 and 4090 and USPHS Grant GM07994.
- excitatory amino acid