INVOLVEMENT OF EXCITATORY AMINO-ACID PATHWAYS IN THE EXPRESSION OF PRECIPITATED OPIOID WITHDRAWAL IN THE ROSTRAL VENTROLATERAL MEDULLA - ANIN-VIVO VOLTAMMETRIC STUDY

Previous studies have shown that catecholaminergic neurons in the rost ral ventrolateral medulla (RVLM) become hyperactive during opioid with drawal. In the present study, the role of excitatory amino acid pathwa ys in the expression of opioid withdrawal in the RVLM was examined by using differential normal pulse voltammetry (DNPV) to measure changes in the catecholamine oxidation current (CA . OC) following naloxone ch allenge in rats treated with acute or chronic morphine. Acute morphine (10 mu g i.c.v.) significantly reduced the CA . OC signal in the RVLM and the mean arterial pressure to 37.1 +/- 6.6% and 21.1 +/- 3.5% bel ow baseline, respectively. Naloxone (1 mg kg(-1) i.v.) reversed the mo rphine effect and produced a significant increase in the CA . OC signa l to 25.6 +/- 15.2% above baseline. In animals treated with chronic mo rphine (10 mu g h(-1) i.c.v., 5 days), naloxone (1 mg kg(-1) i.v.) pro duced a significant increase in the CA . OC signal to 54.2 +/- 16.5% a bove baseline. Both the nonselective excitatory amino acid antagonist, gamma-D-glutamylglycine (DGG, 200 mu g i.c.v.) and the selective NMDA antagonist, D(-)-amino-7-phosphonoheptanoic acid (D-APH, 25 mu g i.c. v.) attenuated the naloxone-induced increase in the CA . OC by 50.7% a nd 46.0% respectively. In morphine naive animals, DGG and D-APH depres sed the CA . OC by 42.8 +/- 8.7% and 17.7 +/- 9.8%, respectively. To t he extent that the CA . OC is an index of neuronal activity, these res ults suggest that RVLM hyperactivity during morphine withdrawal is dep endent, in part, upon activation of NMDA receptors.