Tags

Type your tag names separated by a space and hit enter

Correlated species differences in the effects of cannabinoid ligands on anxiety and on GABAergic and glutamatergic synaptic transmission.
Eur J Neurosci 2007; 25(8):2445-56EJ

Abstract

Cannabinoid ligands show therapeutic potential in a variety of disorders including anxiety. However, the anxiety-related effects of cannabinoids remain controversial as agonists show opposite effects in mice and rats. Here we compared the effects of the cannabinoid agonist WIN-55,212 and the CB1 antagonist AM-251 in CD1 mice and Wistar rats. Special attention was paid to antagonist-agonist interactions, which had not yet been studied in rats. In mice, WIN-55,212 decreased whereas AM-251 increased anxiety. The antagonist abolished the effects of the agonist. In contrast, WIN-55,212 increased anxiety in rats. Surprisingly, the antagonist potentiated this effect. Cannabinoids affect both GABAergic and glutamatergic functions, which play opposite roles in anxiety. We hypothesized that discrepant findings resulted from species differences in the relative responsiveness of the two transmitter systems to cannabinoids. We investigated this hypothesis by studying the effects of WIN-55,212 on evoked hippocampal inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs). IPSCs were one order of magnitude more sensitive to WIN-55,212 in mice than in rats. In mice, IPSCs were more sensitive than EPSCs to WIN-55,212. This is the first study showing that the relative cannabinoid sensitivity of GABA and glutamate neurotransmission is species-dependent. Based on behavioural and electrophysiological findings, we hypothesize that WIN-55,212 reduced anxiety in mice by affecting GABA neurotransmission whereas it increased anxiety in rats via glutamatergic mechanisms. In rats, AM-251 potentiated this anxiogenic effect by inhibiting the anxiolytic GABAergic mechanism. We suggest that the anxiety-related effects of cannabinoids depend on the relative cannabinoid responsiveness of GABAergic and glutamatergic neurotransmission.

Authors+Show Affiliations

Institute of Experimental Medicine, Department of Behavioral Neurobiology, 1450 Budapest, PO Box 67, Hungary. haller@koki.huNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17445240

Citation

Haller, J, et al. "Correlated Species Differences in the Effects of Cannabinoid Ligands On Anxiety and On GABAergic and Glutamatergic Synaptic Transmission." The European Journal of Neuroscience, vol. 25, no. 8, 2007, pp. 2445-56.
Haller J, Mátyás F, Soproni K, et al. Correlated species differences in the effects of cannabinoid ligands on anxiety and on GABAergic and glutamatergic synaptic transmission. Eur J Neurosci. 2007;25(8):2445-56.
Haller, J., Mátyás, F., Soproni, K., Varga, B., Barsy, B., Németh, B., ... Hájos, N. (2007). Correlated species differences in the effects of cannabinoid ligands on anxiety and on GABAergic and glutamatergic synaptic transmission. The European Journal of Neuroscience, 25(8), pp. 2445-56.
Haller J, et al. Correlated Species Differences in the Effects of Cannabinoid Ligands On Anxiety and On GABAergic and Glutamatergic Synaptic Transmission. Eur J Neurosci. 2007;25(8):2445-56. PubMed PMID: 17445240.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Correlated species differences in the effects of cannabinoid ligands on anxiety and on GABAergic and glutamatergic synaptic transmission. AU - Haller,J, AU - Mátyás,F, AU - Soproni,K, AU - Varga,B, AU - Barsy,B, AU - Németh,B, AU - Mikics,E, AU - Freund,T F, AU - Hájos,N, PY - 2007/4/21/pubmed PY - 2007/7/13/medline PY - 2007/4/21/entrez SP - 2445 EP - 56 JF - The European journal of neuroscience JO - Eur. J. Neurosci. VL - 25 IS - 8 N2 - Cannabinoid ligands show therapeutic potential in a variety of disorders including anxiety. However, the anxiety-related effects of cannabinoids remain controversial as agonists show opposite effects in mice and rats. Here we compared the effects of the cannabinoid agonist WIN-55,212 and the CB1 antagonist AM-251 in CD1 mice and Wistar rats. Special attention was paid to antagonist-agonist interactions, which had not yet been studied in rats. In mice, WIN-55,212 decreased whereas AM-251 increased anxiety. The antagonist abolished the effects of the agonist. In contrast, WIN-55,212 increased anxiety in rats. Surprisingly, the antagonist potentiated this effect. Cannabinoids affect both GABAergic and glutamatergic functions, which play opposite roles in anxiety. We hypothesized that discrepant findings resulted from species differences in the relative responsiveness of the two transmitter systems to cannabinoids. We investigated this hypothesis by studying the effects of WIN-55,212 on evoked hippocampal inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs). IPSCs were one order of magnitude more sensitive to WIN-55,212 in mice than in rats. In mice, IPSCs were more sensitive than EPSCs to WIN-55,212. This is the first study showing that the relative cannabinoid sensitivity of GABA and glutamate neurotransmission is species-dependent. Based on behavioural and electrophysiological findings, we hypothesize that WIN-55,212 reduced anxiety in mice by affecting GABA neurotransmission whereas it increased anxiety in rats via glutamatergic mechanisms. In rats, AM-251 potentiated this anxiogenic effect by inhibiting the anxiolytic GABAergic mechanism. We suggest that the anxiety-related effects of cannabinoids depend on the relative cannabinoid responsiveness of GABAergic and glutamatergic neurotransmission. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/17445240/Correlated_species_differences_in_the_effects_of_cannabinoid_ligands_on_anxiety_and_on_GABAergic_and_glutamatergic_synaptic_transmission_ L2 - https://doi.org/10.1111/j.1460-9568.2007.05476.x DB - PRIME DP - Unbound Medicine ER -