Enhanced Glutamatergic Synaptic Plasticity in the Hippocampal CA1 Field of Food-Restricted Rats: Involvement of CB1 Receptors.
The endogenous endocannabinoid system has a crucial role in regulating appetite and feeding behavior in mammals, as well as working memory and reward mechanisms. In order to elucidate the possible role of cannabinoid type-1 receptors (CB1Rs) in the regulation of hippocampal plasticity in animals exposed to food restriction (FR), we limited the availability of food to a 2-h daily period for 3 weeks in Sprague-Dawley rats. FR rats showed a higher long-term potentiation at hippocampal CA1 excitatory synapses with a parallel increase in glutamate release when compared with animals fed ad libitum. FR rats showed a significant increase in the long-term spatial memory determined by Barnes maze. FR was also associated with a decreased inhibitory effect of the CB1R agonist win55,212-2 on glutamatergic field excitatory postsynaptic potentials, together with a decrease in hippocampal CB1R protein expression. In addition, hippocampal brain-derived neurotrophic factor protein levels and mushroom dendritic spine density were significantly enhanced in FR rats. Altogether, our data suggest that alterations of hippocampal CB1R expression and function in FR rats are associated with dendritic spine remodeling and functional potentiation of CA1 excitatory synapses, and these findings are consistent with increasing evidence supporting the idea that FR may improve cognitive functions.
Institute of Neuroscience, National Research Council (CNR), Cittadella Universitaria, Monserrato, Italy.
Giuseppe
G
Talani
Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, University of Cagliari, Monserrato, Italy.
Valentina
V
Licheri
Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, University of Cagliari, Monserrato, Italy.
Francesca
F
Biggio
Department of Biomedical Sciences, University of Cagliari, Monserrato, Italy.
Valentina
V
Locci
Institute of Neuroscience, National Research Council (CNR), Cittadella Universitaria, Monserrato, Italy.
Maria Cristina
MC
Mostallino
Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, University of Cagliari, Monserrato, Italy.
Pietro Paolo
PP
Secci
Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, University of Cagliari, Monserrato, Italy.
Valentina
V
Melis
Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, University of Cagliari, Monserrato, Italy.
Laura
L
Dazzi
Department of Biomedical Sciences, University of Cagliari, Monserrato, Italy.
Gianfranca
G
Carta
Department of Biomedical Science, University of Sassari, Sassari, Italy.
Sebastiano
S
Banni
Institute of Neuroscience, National Research Council (CNR), Cittadella Universitaria, Monserrato, Italy.|Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, University of Cagliari, Monserrato, Italy.
Giovanni
G
Biggio
Institute of Neuroscience, National Research Council (CNR), Cittadella Universitaria, Monserrato, Italy.|Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, University of Cagliari, Monserrato, Italy.
Enrico
E
Sanna
D000818:Animals; D048588:Benzoxazines / Q000008:administration & dosage; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D063387:Cannabinoid Receptor Antagonists / Q000008:administration & dosage; D049229:Dendritic Spines / Q000502:physiology; D063388:Endocannabinoids / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005508:Food Deprivation / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009025:Morpholines / Q000008:administration & dosage; D009281:Naphthalenes / Q000008:administration & dosage; D009473:Neuronal Plasticity / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011720:Pyrazoles / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D000077285:Rimonabant; D065853:Spatial Learning / Q000502:physiology; D065852:Spatial Memory / Q000502:physiology
D048588:Benzoxazines; D019208:Brain-Derived Neurotrophic Factor; D063387:Cannabinoid Receptor Antagonists; D063388:Endocannabinoids; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D018698:Glutamic Acid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077285:Rimonabant