title: Dorsal hippocampus cannabinoid type 1 receptors modulate the expression of contextual fear conditioning in rats: Involvement of local glutamatergic/nitrergic and GABAergic neurotransmissions.
abstract: The cannabinoid receptor type 1 (CB1) is highly expressed in the dorsal portion of hippocampus - a brain region that has been involved in the control of conditioned emotional response (CER) in the contextual fear conditioning (CFC) model. These responses are characterized by increased freezing behavior and autonomic parameters. Moreover, CB1 receptors activation negatively modulate the release of several neurotransmitters, including glutamate and GABA, which also have been related to modulation of CER. Therefore, our aim was to investigate the involvement of CB1 receptors in the dorsal hippocampus on CER expression. Independent groups of male Wistar rats submitted to the contextual fear conditioning received bilateral intra-hippocampal injections (500 nL/side) of the following drugs or vehicle before re-exposure to the aversive context: AM251 (CB1 antagonist; 0.1, 0.3 and 1nmol); AP7 (NMDA antagonist; 1nmol)+AM251 (0.3nmol); NPLA (0.01nmol; nNOS inhibitor)+AM251 (0.3nmol); Bicuculline (1.3pmol; GABAA antagonist)+AM251 (0.1 and 1nmol). In the present paper, AM251 (0.3nmol) increased CER, while this response was prevented by both AP7 and NPLA pretreatment. After pretreatment with Bicuculline, the lower and higher ineffective doses of AM251 were able to increase the CER, supporting the balance between GABAergic and glutamatergic mechanisms controlling this response. Our results suggest that increased CER evoked by CB1 blockade in the dorsal hippocampus depends on NMDA receptor activation and NO formation. Moreover, a fine-tune control promoted by GABAergic and glutamatergic mechanisms in this brain area modulate the CER after CB1 blockade.
authors: Pharmacology Department, Medical School of Ribeirão Preto, University of São Paulo, Av Bandeirantes 3900, Monte Alegre, 14049-900 Ribeirão Preto, São Paulo, Brazil.
authors: Gabriela B L
authors: GB
authors: Spiacci
authors: Pharmacology Department, Medical School of Ribeirão Preto, University of São Paulo, Av Bandeirantes 3900, Monte Alegre, 14049-900 Ribeirão Preto, São Paulo, Brazil.
authors: Leandro S
authors: LS
authors: Antero
authors: Pharmacology Department, Medical School of Ribeirão Preto, University of São Paulo, Av Bandeirantes 3900, Monte Alegre, 14049-900 Ribeirão Preto, São Paulo, Brazil.
authors: Daniel G
authors: DG
authors: Reis
authors: Pharmacology Department, Medical School of Ribeirão Preto, University of São Paulo, Av Bandeirantes 3900, Monte Alegre, 14049-900 Ribeirão Preto, São Paulo, Brazil. Electronic address: sa_lisboa@hotmail.com.
authors: Sabrina F
authors: SF
authors: Lisboa
authors: Pharmacology Department, Medical School of Ribeirão Preto, University of São Paulo, Av Bandeirantes 3900, Monte Alegre, 14049-900 Ribeirão Preto, São Paulo, Brazil. Electronic address: leoresstel@yahoo.com.br.
authors: Leonardo B
authors: LB
authors: Resstel
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003213:Conditioning, Psychological; D004644:Emotions / Q000187:drug effects; D005239:Fear / Q000523:psychology*; D018756:GABA Antagonists / Q000494:pharmacology; D005971:Glutamates / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D018756:GABA Antagonists; D005971:Glutamates; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D009569:Nitric Oxide; C103505:AM 251; D005680:gamma-Aminobutyric Acid; D019001:Nitric Oxide Synthase; D001640:Bicuculline
keywords: Autonomic responses; CB1 receptors; Endocannabinoid system; Freezing behavior; NMDA receptors; Nitric oxide