Deltorphin II enhances extracellular levels of dopamine in the nucleus accumbens via opioid receptor-independent mechanisms.
The effects of the delta2-opioid receptor agonist, deltorphin II, on extracellular levels of dopamine in the rat nucleus accumbens were investigated in awake animals by in vivo brain microdialysis. In agreement with previous studies, perfusion of deltorphin II (50.0 nmol) into the nucleus accumbens significantly increased the extracellular amount of accumbal dopamine. The effect of deltorphin II (50.0 nmol) was not altered by the selective delta2-opioid receptor antagonist, naltriben (1.5 nmol), which alone did not significantly affect the basal levels of dopamine. Selective antagonists of neither the mu-opioid receptors, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH2 (0.15 nmol), nor the delta1-opioid receptors, (E)-7-benzylidenenaltrexone tartrate (0.15 nmol), failed to significantly alter the effects of deltorphin II. The nonselective opioid receptor antagonist, naloxone (0.75 and 1.5 nmol), which alone did not significantly affect the basal levels of dopamine, also failed to affect the effects of deltorphin II. Moreover, under the condition that the sodium channel blocker, tetrodotoxin (0.1 nmol), was perfused continuously into the nucleus accumbens, the deltorphin II-induced increase in extracellular levels of dopamine was reduced by 72%. These results suggest that deltorphin II enhances extracellular dopamine in the nucleus accumbens via opioid receptor-independent, tetrodotoxin-sensitive mechanisms.
Murakawa
Kaoru
K
Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda, Tokyo, 101-8310, Japan.
Hirose
Noriya
N
Takada
Koji
K
Suzuki
Tsutomu
T
Nagase
Hiroshi
H
Cools
Alexander R
AR
Koshikawa
Noriaki
N
D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000502:physiology*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D000779:Anesthetics, Local; D001597:Benzylidene Compounds; D009292:Narcotic Antagonists; D009842:Oligopeptides; D011957:Receptors, Opioid; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; C068868:naltrindole benzofuran; C060209:deltorphin II, Ala(2)-; C077358:7-benzylidenenaltrexone; D009270:Naloxone; D013779:Tetrodotoxin; D013004:Somatostatin; D009271:Naltrexone; D004298:Dopamine