Cannabinoid CB1 receptors control the effects of 5-HT3 neurotransmission on anxiety
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1
Department of Behavioural Neurobiology, Institute of Experimental Medicine, Hungary
Serotonergic fibers originating from the raphe specifically target 5-HT3 receptor-expressing, cholecystokinin-containing GABAergic interneurons in the prefrontal cortex, hippocampus and basolateral amygdala, i.e. brain areas that are tightly involved in the control of emotional responses. The activity of the same neurons is retrogradely inhibited by cannabinoid signaling. This suggests a functional interaction between 5-HT3 neurotransmission and CB1 function. To test this hypothesis, we treated CB1-KO and wild type mice with the specific 5-HT3 agonist 1-(m-chlorophenyl)-biguanide (mCPBG; 1, 3 and 10 mg/kg) and investigated them in the elevated plus-maze test of anxiety 30min later. NMRI mice were also studied. mCPBG significantly decreased anxiety in CB1-KO but not in wild type and NMRI mice. mCPBG did not affect locomotion in any of the strains. We hypothesize that CB1 receptors block GABAergic discharges promoted by 5-HT3 neurotransmission. Hence, 5-HT3 stimulation-induced GABA release was dampened by cannabinoid signaling in normal mice but not in CB1-KOs, where retrograde cannabinoid signaling is absent. Taken together, our findings reveal a functional interaction between 5-HT3 neurotransmission and CB1 signaling, which may be at least partly responsible for the highly inconsistent effects of 5-HT3 ligands in test of anxiety.
Conference:
12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009.
Presentation Type:
Poster Presentation
Topic:
Behavioural neuroscience
Citation:
Mikics
E,
Vas
J,
Aliczki
M and
Haller
J
(2009). Cannabinoid CB1 receptors control the effects of 5-HT3 neurotransmission on anxiety.
Front. Syst. Neurosci.
Conference Abstract:
12th Meeting of the Hungarian Neuroscience Society.
doi: 10.3389/conf.neuro.01.2009.04.252
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Received:
16 Mar 2009;
Published Online:
16 Mar 2009.
*
Correspondence:
Eva Mikics, Department of Behavioural Neurobiology, Institute of Experimental Medicine, Budapest, Hungary, mikics@koki.hu