Buprenorphine and morphine produce equivalent increases in extracellular single unit activity of dopamine neurons in the ventral tegmental area in vivo.
Buprenorphine is a synthetic opioid proposed as a potential treatment for drug abuse. Although buprenorphine is widely considered to be a partial agonist at opioid receptors, little is known of its electrophysiological effects in the central nervous system. Because buprenorphine has been reported to have limited hedonic effects in humans, and since activation of the dopaminergic system is thought to be critical to the reinforcing effects of drugs, we compared the ability of buprenorphine and morphine to activate dopamine neurons. We report here that buprenorphine and morphine are equally effective in increasing the impulse flow of dopamine cells in the ventral tegmental area. Extracellular single unit activity was recorded from dopaminergic (DA) neurons in the ventral tegmental area (VTA) of chloral hydrate anesthetized rats. Standard physiological and anatomical criteria were used to identify DA neurons. Systemic injection of buprenorphine (5-200 micrograms/kg, i.v.) and morphine (1-10 mg/kg, i.v.) produced equal magnitudes of activation in a similar subset of DA neurons in the VTA (buprenorphine: 173%; morphine: 164%). Unlike morphine, the activation by buprenorphine was not reversed by the opioid antagonist naloxone (50-100 micrograms/kg, i.v.), but this is consistent with the known pharmacodynamics of buprenorphine at opioid receptors. These studies demonstrate that acute administration of buprenorphine has morphine-like effects on the impulse activity of DA neurons. The implications for use of buprenorphine as a clinical treatment for drug abuse are discussed.
Grant
S J
SJ
Department of Psychology, University of Delaware, Newark 19716.
Sonti
G
G
D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology*; D004298:Dopamine / Q000032:analysis; D005110:Extracellular Space; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D002047:Buprenorphine; D009020:Morphine; D004298:Dopamine