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Modulation of anxiety by acute blockade and genetic deletion of the CB(1) cannabinoid receptor in mice together with biogenic amine changes in the forebrain.
Behav Brain Res. 2009 Jun 08; 200(1):60-7.BB

Abstract

The CB(1) cannabinoid receptor has been implicated in the control of fear and anxiety. We investigated the effects of genetic and pharmacological blockade of the CB(1) cannabinoid receptor on the behaviour of CD1 mice using three different ethological models of fear and anxiety (elevated T-maze and plus-maze and open field test of emotionality). Furthermore, we measured tissue levels of noradrenalin (NA), dopamine (DA), serotonin (5-HT) and their metabolites in several forebrain regions, i.e. prefrontal cortex, hippocampus, septum, dorsal and ventral striatum to examine the relationship between CB(1) receptor manipulation and monoaminergic neurotransmission. The major findings can be summarized as follows: the CB(1) receptor antagonist SR141617A (rimonabant) modulated anxiety in a dose-dependent manner. At a dose of 3 mg/kg i.p., the compound consistently increased anxiety parameters in all of the three different anxiety tests applied, while a lower dosage of 1mg/kg had no such effect. The neurochemical evaluation of the mice administered 3mg/kg SR141617A revealed increases in the concentrations of DOPAC and 5-HIAA in the dorsal striatum, elevated DA levels in the hippocampus and reduced dopamine turnover in the septum. Furthermore, these animals had a higher HVA/DA turnover in the frontal cortex. CB(1) receptor knockout mice as well as mice treated with the selective CB(1) receptor antagonist AM251 (3 mg/kg; i.p.) did not display any significant alterations in anxiety-related behaviour as measured with the elevated plus-maze and open field test of emotionality, respectively. Our findings support the general idea of a SR141617A-sensitive receptive site that is different from the 'classical' CB(1) receptor and that has a pivotal role in the regulation of different psychological functions. However, with regard to its functional significance in terms of anxiety our findings suggest that under physiological conditions this receptive site seems to be involved in the control of anxiolysis rather than anxiogenesis as suggested previously.

Authors+Show Affiliations

School of Psychology, Neuroscience Research Unit, University of Hertfordshire, College Lane, Hatfield, Herts AL109AB, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19162082

Citation

Thiemann, Gunnar, et al. "Modulation of Anxiety By Acute Blockade and Genetic Deletion of the CB(1) Cannabinoid Receptor in Mice Together With Biogenic Amine Changes in the Forebrain." Behavioural Brain Research, vol. 200, no. 1, 2009, pp. 60-7.
Thiemann G, Watt CA, Ledent C, et al. Modulation of anxiety by acute blockade and genetic deletion of the CB(1) cannabinoid receptor in mice together with biogenic amine changes in the forebrain. Behav Brain Res. 2009;200(1):60-7.
Thiemann, G., Watt, C. A., Ledent, C., Molleman, A., & Hasenöhrl, R. U. (2009). Modulation of anxiety by acute blockade and genetic deletion of the CB(1) cannabinoid receptor in mice together with biogenic amine changes in the forebrain. Behavioural Brain Research, 200(1), 60-7. https://doi.org/10.1016/j.bbr.2008.12.035
Thiemann G, et al. Modulation of Anxiety By Acute Blockade and Genetic Deletion of the CB(1) Cannabinoid Receptor in Mice Together With Biogenic Amine Changes in the Forebrain. Behav Brain Res. 2009 Jun 8;200(1):60-7. PubMed PMID: 19162082.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of anxiety by acute blockade and genetic deletion of the CB(1) cannabinoid receptor in mice together with biogenic amine changes in the forebrain. AU - Thiemann,Gunnar, AU - Watt,Carly A, AU - Ledent,Catherine, AU - Molleman,Areles, AU - Hasenöhrl,Rüdiger U, Y1 - 2009/01/08/ PY - 2008/01/10/received PY - 2008/12/21/revised PY - 2008/12/23/accepted PY - 2009/1/24/entrez PY - 2009/1/24/pubmed PY - 2009/6/19/medline SP - 60 EP - 7 JF - Behavioural brain research JO - Behav Brain Res VL - 200 IS - 1 N2 - The CB(1) cannabinoid receptor has been implicated in the control of fear and anxiety. We investigated the effects of genetic and pharmacological blockade of the CB(1) cannabinoid receptor on the behaviour of CD1 mice using three different ethological models of fear and anxiety (elevated T-maze and plus-maze and open field test of emotionality). Furthermore, we measured tissue levels of noradrenalin (NA), dopamine (DA), serotonin (5-HT) and their metabolites in several forebrain regions, i.e. prefrontal cortex, hippocampus, septum, dorsal and ventral striatum to examine the relationship between CB(1) receptor manipulation and monoaminergic neurotransmission. The major findings can be summarized as follows: the CB(1) receptor antagonist SR141617A (rimonabant) modulated anxiety in a dose-dependent manner. At a dose of 3 mg/kg i.p., the compound consistently increased anxiety parameters in all of the three different anxiety tests applied, while a lower dosage of 1mg/kg had no such effect. The neurochemical evaluation of the mice administered 3mg/kg SR141617A revealed increases in the concentrations of DOPAC and 5-HIAA in the dorsal striatum, elevated DA levels in the hippocampus and reduced dopamine turnover in the septum. Furthermore, these animals had a higher HVA/DA turnover in the frontal cortex. CB(1) receptor knockout mice as well as mice treated with the selective CB(1) receptor antagonist AM251 (3 mg/kg; i.p.) did not display any significant alterations in anxiety-related behaviour as measured with the elevated plus-maze and open field test of emotionality, respectively. Our findings support the general idea of a SR141617A-sensitive receptive site that is different from the 'classical' CB(1) receptor and that has a pivotal role in the regulation of different psychological functions. However, with regard to its functional significance in terms of anxiety our findings suggest that under physiological conditions this receptive site seems to be involved in the control of anxiolysis rather than anxiogenesis as suggested previously. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/19162082/Modulation_of_anxiety_by_acute_blockade_and_genetic_deletion_of_the_CB_1__cannabinoid_receptor_in_mice_together_with_biogenic_amine_changes_in_the_forebrain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(09)00003-5 DB - PRIME DP - Unbound Medicine ER -