Glutamate in opioid dependence.
The present review will concentrate on a discussion of recent investigations which implicate a critical linkage of three facets of the central nervous system mediation of opioid dependence, as evidenced by expression of acutely-precipitated withdrawal events. These are the kappa-opioid receptor subtype, the glutamatergic neuronal system and a specific brain locus, the locus coeruleus. The impetus for this line of investigation derives from a recognition that opioid analgesics, such as butorphanol (Stadol), exhibit a markedly different profile of activity at opioid receptors than does morphine yet have abuse liability and cause dependence readily. Emphasis will be placed on demonstration of a rodent model in which butorphanol administration induces dependence through a unique (in comparison with morphine) activation of the kappa-opioid receptor. The use of in vivo microdialysis techniques clearly identifies, in this model, that acutely-precipitated withdrawal from dependence on butorphanol results in focal increases in extracellular levels of glutamate within the locus coeruleus, and that the withdrawal syndrome can be mimicked by intracerebroventricular administration of exogenous glutamate, acting through the N-methyl-D-aspartate glutamate receptor subtype. The data confirm the participation of glutamate as a general phenomenon in opioid dependence, identify the locus coeruleus as a primary site for glutamatergic mediation of dependence, and suggest novel aspects to the neuropharmacology of opioid dependence with respect to the role of the kappa-opioid receptor.
Ho
I K
IK
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Feng
Y Z
YZ
Tokuyama
S
S
Hoshi
K
K
Rockhold
R W
RW
D000701:Analgesics, Opioid; D000818:Animals; D002077:Butorphanol; D018698:Glutamic Acid / Q000502:physiology*; D008125:Locus Coeruleus / Q000502:physiology; D017551:Microdialysis; D009293:Opioid-Related Disorders; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000502:physiology; D013375:Substance Withdrawal Syndrome
D000701:Analgesics, Opioid; D017473:Receptors, Opioid, kappa; D018698:Glutamic Acid; D002077:Butorphanol