Synergistic antidepressant-like action of gaboxadol and escitalopram
Authors: Bjarke Ebert
Trine Christensen
Ove Wiborg
Adeline Etievant
Nasser Haddjeri
Cécile Bétry
Ouissame Mnie-Filali
Journal: European Neuropsychopharmacology (2012)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: depression; GABAergic; monoaminergic; gaboxadol; escitalopram
Affiliations: Centre for Psychiatric Research, Aarhus University Hospital, Skovagervej 2, 8240 Risskov, Denmark.

Abstract:  According to current theories on the etiopathogenesis and pathophysiology of depression, both GABAergic and monoaminergic transmitter systems are perturbed. Consequently, the present study addressed the putative antidepressant action of the sedative-hypnotic GABAA receptor agonist, gaboxadol, separately and in combination with the selective serotonin reuptake inhibitor (SSRI) escitalopram. The rat chronic mild stress model was used to test the chronic antidepressant properties of gaboxadol in this depression model. Sucrose intake used as a read-out on anhedonic-like behavior indicated that the drug response rate for gaboxadol (5 mg/kg/day, i.p.) was similar to that measured for escitalopram (5 mg/kg/day, i.p.), however, the rate increased when the two drugs were co-administered, suggesting a synergistic action. Using in vivo electrophysiological recordings in dorsal raphe nucleus (DRN) of anesthetised rats, the present results showed that one week treatment with gaboxadol (5 mg/kg/day, i.p.) or with escitalopram (5 mg/kg/day, i.p.), followed by a 24 h washout period, did not affect DRN 5-HT neuronal firing per se, but in rats treated with both drugs for one week, the firing rate of DRN 5-HT neurons was significantly increased. Immunohistochemical estimations of cell proliferation in the hippocampal dentate gyrus did not reveal any effect of gaboxadol on chronic mild stressed rats, indicating that neurogenesis per se is not systematically associated with recovery from anhedonic-like behavior. Taken together, our data reveal for the first time an antidepressant action of gaboxadol and indicate a synergistic mechanism, regarding rapid onset of action and efficacy, when co-administered with escitalopram. 

Retracted: No

PubPeer comments:
 The immunostaining image in Figure 3 or this paper is a pretty one. ![file] So much so that the authors seem to have used it on at least two other occasions. Some work has been done on the image between publications - to obscure the fact that it is the same image, a cynical person might suggest. In this particular instance the brightness exposure has been lowered to make the image darker, and compared to Jayatissa et al. (2009) the image has been rotated and stretched. ![file] Reusing an image without proper attribution is, in itself, somewhat problematic. But the image is said to represent animals undergoing different treatments in all three papers. This is confusing. If the authors followed their methods they should have ample images to choose from in each new experiment. So why did they have to resort to showing a several-years-old image instead? , 
 I forgot to include links to the other two papers: https: pubpeer.com publications 3086D6AA6B1E26F75A8B1DD5226723 https: pubpeer.com publications A71A48873C134C832DF656F6743E4E Moreover, I will note that the above image has also been published as part of the review:  Chronic mild stress for modeling anhedonia (2013), Wiborg O. In the review it is alleged that the image was actually obtained in an investigation that was published in 2006. ![file] This could be the author confusing the references. And who could blame him? It seems truly puzzling where these images were *actually* obtained. ,