title: Ketamine modulates catecholamine transmission in the bed nucleus of stria terminalis: The possible role of this region in the antidepressant effects of ketamine.
abstract: Since the therapeutic treatment of depression is far from being satisfactory, new therapeutic strategies ought to be pursued. In addition, further investigation on brain areas involved in the action mechanism of antidepressants can shed light on the aetiology of depression. We have previously reported that typical and atypical antidepressants strongly stimulate catecholamine transmission in the bed nucleus of stria terminalis (BNST). In this study, we have built on that work to examine the effect of ketamine, an unusual antidepressant that can produce a fast-acting and long-lasting antidepressant effect after administration of a single sub-anaesthetic dose. Ketamine is an antagonist of the ionotropic N-methyl-D-aspartate (NMDA) receptor but can also act through its metabolite (2R-6R)-hydroxynorketamine. Using the microdialysis technique in freely moving rats, we monitored the acute effect of ketamine on catecholamine release in the BNST to gain clues to its prompt antidepressant effect. Male Sprague-Dawley rats were implanted with a microdialysis probe in the BNST and 48h later, were injected with ketamine (10, 20, and 40mg/kg, i.p.). Ketamine increased norepinephrine (127%, 155%, 186%) and dopamine (114%, 156%, 176%) extracellular concentration above basal in a time and dose dependent manner, without significantly modifying motility. Since the effect of ketamine, although lower, was not substantially different from that produced by classical antidepressants, we suggest that catecholamine increase in BNST is not likely to be related to a rapid ketamine antidepressant effect, though it might be related to its performance in predictive tests of antidepressant properties.
authors: Department of Biomedical Sciences, University of Cagliari, Via Ospedale 72, 09126 Cagliari, Italy.
authors: Roberto
authors: R
authors: Cadeddu
authors: Department of Biomedical Sciences, University of Cagliari, Via Ospedale 72, 09126 Cagliari, Italy.
authors: Dragana
authors: D
authors: Jadzic
authors: Department of Biomedical Sciences, University of Cagliari, Via Ospedale 72, 09126 Cagliari, Italy; Neuroscience Institute, Section of Cagliari, National Research Council of Italy - CNR, Cagliari, Italy.
authors: Ezio
authors: E
authors: Carboni
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012686:Septal Nuclei / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D002395:Catecholamines; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine
keywords: Bed nucleus of stria terminalis; Dopamine; Ketamine; Microdialysis; Norepinephrine