Stimulation of in vivo dopamine transmission and intravenous self-administration in rats and mice by JWH-018, a Spice cannabinoid.
Neuropharmacology. 2015-12-01; 99: 705-714
DOI: 10.1016/j.neuropharm.2015.08.041
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1. Neuropharmacology. 2015 Dec;99:705-14. doi: 10.1016/j.neuropharm.2015.08.041.
Epub 2015 Oct 23.
Stimulation of in vivo dopamine transmission and intravenous self-administration
in rats and mice by JWH-018, a Spice cannabinoid.
De Luca MA(1), Bimpisidis Z(2), Melis M(2), Marti M(3), Caboni P(4), Valentini
V(5), Margiani G(2), Pintori N(2), Polis I(6), Marsicano G(7), Parsons LH(6), Di
Chiara G(8).
Author information:
(1)Department of Biomedical Sciences, University of Cagliari, Italy; INN,
National Institute of Neuroscience, Italy. Electronic address: .
(2)Department of Biomedical Sciences, University of Cagliari, Italy.
(3)INN, National Institute of Neuroscience, Italy; Department of Life Sciences
and Biotechnology, University of Ferrara, Italy.
(4)Department of Life and Environmental Sciences, University of Cagliari, Italy.
(5)Department of Biomedical Sciences, University of Cagliari, Italy; INN,
National Institute of Neuroscience, Italy; Centre of Excellence « Neurobiology of
Addiction », Italy.
(6)The Scripps Research Institute, La Jolla, CA, USA.
(7)Neurocentre Magendie, University of Bordeaux, France.
(8)Department of Biomedical Sciences, University of Cagliari, Italy; INN,
National Institute of Neuroscience, Italy; CNR Institute of Neuroscience,
Cagliari Section, Italy; Centre of Excellence « Neurobiology of Addiction », Italy.
The synthetic cannabinoid 1-pentyl-3-(1-naphthoyl)-indole (JWH-018) has been
detected in about 140 samples of a smokable herbal mixture termed « Spice ».
JWH-018 is a CB1 and CB2 agonist with a higher affinity than Δ9-THC. In order to
investigate the neurobiological substrates of JWH-018 actions, we studied by
microdialysis in freely moving rats the effect of JWH-018 on extracellular
dopamine (DA) levels in the nucleus accumbens (NAc) shell and core and in the
medial prefrontal cortex (mPFC). JWH-018, at the dose of 0.25 mg/kg i.p.,
increased DA release in the NAc shell but not in the NAc core and mPFC. Lower
(0.125 mg/kg) and higher doses (0.50 mg/kg) were ineffective. These effects were
blocked by CB1 receptor antagonists (SR-141716A and AM 251) and were absent in
mice lacking the CB1 receptor. Ex vivo whole cell patch clamp recordings from rat
ventral tegmental area (VTA) DA neurons showed that JWH-018 decreases
GABAA-mediated post-synaptic currents in a dose-dependent fashion suggesting that
the stimulation of DA release observed in vivo might result from disinhibition of
DA neurons. In addition, on the « tetrad » paradigm for screening cannabinoid-like
effects (i.e., hypothermia, analgesia, catalepsy, hypomotility), JWH-018, at
doses of 1 and 3 mg/kg i.p., produced CB1 receptor-dependent behavioural effects
in rats. Finally, under appropriate experimental conditions, rats (20 μg/kg/inf
i.v., FR3; nose-poking) and mice (30 μg/kg/inf i.v., FR1; lever-pressing)
self-administer intravenously JWH-018. In conclusion, JWH-018 shares with the
active ingredient of Marijuana, Δ9-THC, CB1-dependent reinforcing and DA
stimulant actions.
Copyright © 2015 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.neuropharm.2015.08.041
PMID: 26327678 [Indexed for MEDLINE]