Harvey 2006 Increased hippocampal nitric oxide synthase activity and stress responsiveness after imipramine discontinuation: role of 5HT 2A/C-receptor

[Altostrata]

Possible neurochemical basis for antidepressant withdrawal syndrome. Also see Harvey 2003 Neurobiology of antidepressant withdrawal

 

Metab Brain Dis. 2006 Sep;21(2-3):211-20. Epub 2006 Jul 22.

Increased hippocampal nitric oxide synthase activity and stress responsiveness after imipramine discontinuation: role of 5HT 2A/C-receptors.

Harvey BH, Retief R, Korff A, Wegener G.

 

Source

 

School of Pharmacy Pharmacology, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa. fklbhh@puk.ac.za

 

Abstract at http://www.ncbi.nlm.nih.gov/pubmed/16865538 Full text PDF here.

 

Chronic depressive illness may cause shrinkage of the hippocampus with stress-induced release of glutamate and nitric oxide possibly causally linked to this pathology. Poor antidepressant compliance may contribute to this pathology as well as to long term morbidity. However, antidepressant withdrawal-associated symptoms in depressed patients often reflect hyperserotonergia. The effect of chronic imipramine (IMI; 15 mg/kg/d ip x 3wks) treatment and withdrawal on swim stress responsiveness was studied in Sprague-Dawley rats together with assay of hippocampal NO synthase (NOS) activity. The dependence of any biobehavioral changes following IMI withdrawal on 5HT(2A/C) receptor-mediated events was studied using the 5HT(2A/C) receptor antagonist, ritanserin (RIT; 4 mg/kg/day ip x 7 days), administered alone or during IMI withdrawal. IMI significantly inhibited the situational stress response to forced swimming while also significantly decreasing NOS activity. IMI withdrawal was associated with a significant increase in swim immobility together with a significant increase in NOS activity compared to both control and IMI-treated groups. RIT re-established the anti-immobility effects and reversed NOS hyper-function during IMI withdrawal, although alone it increased NOS activity. Antidepressant discontinuation therefore increases stress responsiveness together with disinhibition of hippocampal NOS through a mechanism involving 5HT(2A/C) receptor activation. The resulting increased nitrergic activity may have significant implications for depressive illness and its treatment.

[Barbarannamated]

Interesting/

Did ritanserin ever make it to market (Q)

 

Sorry /punctuation not working again/can't keep ahead of my electronics

[Altostrata]

Google and ye shall find.