Implication of dopaminergic projection from the ventral tegmental area to the anterior cingulate cortex in μ-opioid-induced place preference.
Despite the importance of prefrontal cortical dopamine in modulating reward, little is known about the implication of the specific subregion of prefrontal cortex in opioid reward. We investigated the role of neurons projecting from the ventral tegmental area (VTA) to the anterior cingulate cortex (ACG) in opioid reward. Microinjection of the retrograde tracer fluorogold (FG) into the ACG revealed several retrogradely labelled cells in the VTA. The FG-positive reactions were noted in both tyrosine hydroxylase (TH)-positive and -negative VTA neurons. The released levels of dopamine and its major metabolites in the ACG were increased by either the electrical stimulation of VTA neurons or microinjection of a selective μ-opioid receptor (MOR) agonist, (D-Ala²,N-MePhe⁴,Gly-ol⁵) enkephalin (DAMGO), into the VTA. MOR-like immunoreactivity was seen in both TH-positive and -negative VTA neurons projecting to the ACG. The conditioned place preference induced by intra-VTA injection of DAMGO was significantly attenuated by chemical lesion of dopaminergic terminals in the ACG. The depletion of dopamine in the ACG induced early extinction of μ-opioid-induced place preference. The levels of phosphorylated DARPP32 (Thr34) and phosphorylated CREB (Ser133) were increased in the ACG of rats that had maintained the morphine-induced place preference, whereas the increases of these levels induced by morphine were blocked by pre-treatment of a selective dopamine D1 receptor antagonist SCH23390. These findings suggest that VTA-ACG transmission may play a crucial role in the acquisition and maintenance of μ-opioid-induced place preference. The activation of DARPP32 and CREB through dopamine D1 receptors in the ACG could be implicated in the maintenance of μ-opioid-induced place preference.
Narita
Minoru
M
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan. narita@hoshi.ac.jp
Matsushima
Yuki
Y
Niikura
Keiichi
K
Narita
Michiko
M
Takagi
Shigemi
S
Nakahara
Kae
K
Kurahashi
Kana
K
Abe
Minako
M
Saeki
Mai
M
Asato
Megumi
M
Imai
Satoshi
S
Ikeda
Kazutaka
K
Kuzumaki
Naoko
N
Suzuki
Tsutomu
T
D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D006179:Gyrus Cinguli / Q000187:drug effects*; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D009042:Motivation / Q000187:drug effects*; D009415:Nerve Net / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000819:agonists*; D009435:Synaptic Transmission / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000187:drug effects*
D001552:Benzazepines; D017362:Cyclic AMP Response Element-Binding Protein; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497930:Ppp1r1b protein, rat; D017447:Receptors, Dopamine D1; D017450:Receptors, Opioid, mu; C534628:SCH 23390; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004298:Dopamine