Cannabinoids reward sensitivity in a neurodevelopmental animal model of schizophrenia: a brain stimulation reward study.
European Neuropsychopharmacology. 2014-09-01; 24(9): 1534-1545
DOI: 10.1016/j.euroneuro.2014.07.003
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Gallo A(1), Bouchard C(2), Fortier E(2), Ducrot C(2), Rompré PP(3).
Author information:
(1)Faculté de médecine, Département de Psychiatrie, Université de Montréal,
Montréal, Québec, Canada.
(2)Faculté de médecine, Département de Neurosciences, Université de Montréal,
Montréal, Québec, Canada.
(3)Faculté de médecine, Département de Neurosciences, Université de Montréal,
Montréal, Québec, Canada; FRQ-S Research Center in Behavioural Neurobiology,
Concordia University, Montréal, Québec, Canada. Electronic address:
.
The comorbidity schizophrenia and cannabis has a high prevalence. The consumption
of cannabis is ten times higher among schizophrenia patients, suggesting that
these patients could be differentially sensitive to its motivational effects. To
study this question, we investigated the motivational effects of cannabinoid
agonists using the brain stimulation reward paradigm and a neurodevelopmental
model of schizophrenia: neonatal ventral hippocampus lesions (NVHL). Using the
curve-shift paradigm, we first compared the effect single dose (0.75mg/kg) of
amphetamine in sham and NVHL rats on reward and operant responding. Then, in
different groups of NVHL and sham rats, we studied the effect of
delta-9-tetrahydrocannabinnol (THC, 0.5mg/kg, i.p.) and WIN55,212-2 (WIN, 1 and
3mg/kg, i.p.) Rats were initially trained to self-administer an electrical
stimulation to the posterio-medial mesencephalon. Once responding was stable,
reward threshold defined as the frequency required to induce a half maximum
response rate was measured before and after injection of the drug or the vehicle.
Results show that amphetamine enhanced reward in sham and NVHL rats, an effect
that was shorter in duration in NVHL rats. THC produced a weak attenuation of
reward in sham rats while WIN produced a dose-dependent attenuation in NVHL; the
attenuation effect of WIN was blocked by the cannabinoid antagonist, AM251. WIN
also produced an attenuation of performance in sham and NVHL rats, and this
effect was partially prevented by AM251. These results provide the additional
evidence that the motivational effect of cannabinoids is altered in animals with
a schizophrenia-like phenotype.
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