TY - JOUR
T1 - The effects of Δ9-tetrahydrocannabinol on potassium-evoked release of dopamine in the rat caudate nucleus
T2 - an in vivo electrochemical and in vivo microdialysis study
AU - Ton, Jean Max Ng Cheong
AU - Gerhardt, Greg A.
AU - Friedemann, Marilyn
AU - Etgen, Anne M.
AU - Rose, Greg M.
AU - Sharpless, Nansie S.
AU - Gardner, Eliot L.
PY - 1988/6/7
Y1 - 1988/6/7
N2 - The effect of systemically administered Δ9-tetrahydrocannabinol (THC), the psychoactive ingredient marijuana, on the potassium-evoked release of dopamine (DA) was examined in the neostriatum of the chloral hydrate anesthetized rat. Both in vivo electrochemical and in vivo microdialysis techniques were employed. A low dose of THC (0.5 mg/kg, i.p.) increased the time course of potassium-evoked in vivo electrochemical signals corresponding to released extracellular DA. In vivo microdialysis showed an increase in potassium-evoked DA release following 0.5 and 2.0 mg/kg doses of THC. Potassium-evoked electrochemical signals corresponding to released extracellular DA were augmented in time course following i.p. administration (5.0 mg/kg) of nomifensine, a recognized and potent catecholaminergic reuptake blocker. In addition, in vivo brain microdialysis studies of nomifensine (5.0 mg/kg i.p.) on neostriatal potassium-evoked DA release showed that DA levels were augmented in magnitude over the time course of the microdialysis. Taken together, these studies indicate that THC has a potent presynaptic augmenting effect on at least the neostriatal portions of the mesotelencephalic DA system in the rat, although the possibility that this effect could be mediated transsynaptically cannot be ruled out. Given the previous extensive evidence for an involvement of portions of the mesotelencephalic DA system in mediating the reinforcing and euphorigenic properties of many classes of abused drugs, and in mediating direct electrical brain stimulation reward, we suggest that the presently demonstrated effects of THC on forebrain dopamine function may be related to marijuana's euphorigenic properties and, thus, to its abuse potential.
AB - The effect of systemically administered Δ9-tetrahydrocannabinol (THC), the psychoactive ingredient marijuana, on the potassium-evoked release of dopamine (DA) was examined in the neostriatum of the chloral hydrate anesthetized rat. Both in vivo electrochemical and in vivo microdialysis techniques were employed. A low dose of THC (0.5 mg/kg, i.p.) increased the time course of potassium-evoked in vivo electrochemical signals corresponding to released extracellular DA. In vivo microdialysis showed an increase in potassium-evoked DA release following 0.5 and 2.0 mg/kg doses of THC. Potassium-evoked electrochemical signals corresponding to released extracellular DA were augmented in time course following i.p. administration (5.0 mg/kg) of nomifensine, a recognized and potent catecholaminergic reuptake blocker. In addition, in vivo brain microdialysis studies of nomifensine (5.0 mg/kg i.p.) on neostriatal potassium-evoked DA release showed that DA levels were augmented in magnitude over the time course of the microdialysis. Taken together, these studies indicate that THC has a potent presynaptic augmenting effect on at least the neostriatal portions of the mesotelencephalic DA system in the rat, although the possibility that this effect could be mediated transsynaptically cannot be ruled out. Given the previous extensive evidence for an involvement of portions of the mesotelencephalic DA system in mediating the reinforcing and euphorigenic properties of many classes of abused drugs, and in mediating direct electrical brain stimulation reward, we suggest that the presently demonstrated effects of THC on forebrain dopamine function may be related to marijuana's euphorigenic properties and, thus, to its abuse potential.
KW - 3,4-Dihydroxyphenylethylamine
KW - Brain reward
KW - Cannabinoid
KW - Cannabis
KW - Caudate nucleus
KW - Dopamine
KW - In vivo electrochemistry
KW - In vivo microdialysis
KW - Marijuana
KW - Neostriatum
KW - Potassium
KW - Rat
KW - Δ-Tetrahydrocannabinol
UR - http://www.scopus.com/inward/record.url?scp=0023893398&partnerID=8YFLogxK
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U2 - 10.1016/0006-8993(88)90749-4
DO - 10.1016/0006-8993(88)90749-4
M3 - Article
C2 - 2855215
AN - SCOPUS:0023893398
SN - 0006-8993
VL - 451
SP - 59
EP - 68
JO - Brain Research
JF - Brain Research
IS - 1-2
ER -