title: Involvement of the cannabinoid CB1 receptor in modulation of dopamine output in the prefrontal cortex associated with food restriction in rats.
abstract: Increase in dopamine output on corticolimbic structures, such as medial prefrontal cortex (mPFC) and nucleus accumbens, has been related to reward effects associated with palatable food or food presentation after a fasting period. The endocannabinoid system regulates feeding behavior through a modulatory action on different neurotransmitter systems, including the dopaminergic system. To elucidate the involvement of type 1 cannabinoid receptors in the regulation of dopamine output in the mPFC associated with feeding in hungry rats, we restricted the food availability to a 2-h period daily for 3 weeks. In food-restricted rats the extracellular dopamine concentration in the mPFC increased starting 80 min before food presentation and returned to baseline after food removal. These changes were attenuated in animals treated with the CB1 receptor antagonist SR141716. To better understand how food restriction can change the response of mesocortical dopaminergic neurons, we studied several components of the neuronal circuit that regulates dopamine output in the mPFC. Patch-clamp experiments revealed that the inhibitory effect of the CB1 receptor agonist WIN 55,212-2 on GABAergic sIPSC frequency was diminished in mPFC neurons of FR compared to fed ad libitum rats. The basal sIPSC frequency resulted reduced in mPFC neurons of food-restricted rats, suggestive of an altered regulation of presynaptic GABA release; these changes were accompanied by an enhanced excitability of mPFC and ventral tegmental area neurons. Finally, type 1 cannabinoid receptor expression in the mPFC was reduced in food-restricted rats. Together, our data support an involvement of the endocannabinoid system in regulation of dopamine release in the mPFC through changes in GABA inhibitory synapses and suggest that the emphasized feeding-associated increase in dopamine output in the mPFC of food-restricted rats might be correlated with an altered expression and function of type 1 cannabinoid receptor in this brain region.
authors.affiliation: Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, Centre of Excellence for the Neurobiology of Dependence, University of Cagliari, Monserrato, Cagliari, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Dazzi
authors.affiliation: Institute of Neuroscience, National Research Council, Monserrato, Cagliari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Talani
authors.affiliation: Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, Centre of Excellence for the Neurobiology of Dependence, University of Cagliari, Monserrato, Cagliari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Biggio
authors.affiliation: Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, Centre of Excellence for the Neurobiology of Dependence, University of Cagliari, Monserrato, Cagliari, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Utzeri
authors.affiliation: Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, Centre of Excellence for the Neurobiology of Dependence, University of Cagliari, Monserrato, Cagliari, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Lallai
authors.affiliation: Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, Centre of Excellence for the Neurobiology of Dependence, University of Cagliari, Monserrato, Cagliari, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Licheri
authors.affiliation: Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, Centre of Excellence for the Neurobiology of Dependence, University of Cagliari, Monserrato, Cagliari, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Lutzu
authors.affiliation: Institute of Neuroscience, National Research Council, Monserrato, Cagliari, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mostallino
authors.affiliation: Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, Centre of Excellence for the Neurobiology of Dependence, University of Cagliari, Monserrato, Cagliari, Italy.
authors.forename: Pietro Paolo
authors.initials: PP
authors.lastname: Secci
authors.affiliation: Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, Centre of Excellence for the Neurobiology of Dependence, University of Cagliari, Monserrato, Cagliari, Italy; Institute of Neuroscience, National Research Council, Monserrato, Cagliari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Biggio
authors.affiliation: Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, Centre of Excellence for the Neurobiology of Dependence, University of Cagliari, Monserrato, Cagliari, Italy; Institute of Neuroscience, National Research Council, Monserrato, Cagliari, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Sanna
mesh_terms: D000818:Animals; D059031:Anticipation, Psychological / Q000187:drug effects; D004032:Diet; D004298:Dopamine / Q000378:metabolism*; D005106:Exploratory Behavior / Q000187:drug effects; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008024:Ligands; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077285:Rimonabant; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D008024:Ligands; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D005680:gamma-Aminobutyric Acid; D000077285:Rimonabant; D004298:Dopamine