Involvement of excitatory amino acid pathways in the expression of precipitated opioid withdrawal in the rostral ventrolateral medulla: an in vivo voltammetric study.
Previous studies have shown that catecholaminergic neurons in the rostral ventrolateral medulla (RVLM) become hyperactive during opioid withdrawal. In the present study, the role of excitatory amino acid pathways in the expression of opioid withdrawal in the RVLM was examined by using differential pulse voltammetry (DNPV) to measure changes in the catecholamine oxidation current (CA.OC) following naloxone challenge in rats treated with acute or chronic morphine. Acute morphine (10 micrograms 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% below baseline, respectively. Naloxone (1 mg kg-1 i.v.) reversed the morphine effect and produced a significant increase in the CA.OC signal to 25.6 +/- 15.2% above baseline. In animals treated with chronic morphine (10 micrograms h-1 i.c.v., 5 days), naloxone (1 mg kg-1 i.v.) produced a significant increase in the CA.OC signal to 54.2 +/- 16.5% above baseline. Both the nonselective excitatory amino acid antagonist, gamma-D-glutamylglycine (DGG, 200 micrograms i.c.v.) and the selective NMDA antagonist, D(-)-amino-7-phosphonoheptanoic acid (D-APH, 25 micrograms i.c.v.) attenuated the naloxone-induced increase in the CA.OC by 50.7% and 46.0% respectively. In morphine naive animals, DGG and D-APH depressed the CA.OC by 42.8 +/- 8.7% and 17.7 +/- 9.8%, respectively. To the extent that the CA.OC is an index of neuronal activity, these results suggest that RVLM hyperactivity during morphine withdrawal is dependent, in part, upon activation of NMDA receptors.
Wang
L
L
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
Milne
B
B
Jhamandas
K
K
D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D004594:Electrophysiology; D018846:Excitatory Amino Acids / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000378:metabolism*; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013997:Time Factors
D002395:Catecholamines; D018846:Excitatory Amino Acids; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine