Effect of paroxetine and venlafaxine on mice exposed to chronic mild stress

The role of gamma-amino butyric acid [GABA] in mood disorders and its interaction with serotonin [5-HT] and norepinephrine [NE] systems is worthy of further study. Many studies reported that plasma GABA levels are relatively reduced in depressed patients. The present study investigated the alteration of GABA content by long-term antidepressant treatment with either paroxetine as one of the selective serotonin r-euptake inhibitors [SSRIs] or venlafaxine as a serotonin-norepinephrine re-uptake inhibitor [SNRI] in the frontal cortex [F.Cx] [as a brain region crucial for the control of emotion and cognition] obtained from male mice exposed to chronic mild stress[CMS]-induced anhedonia. The long term behavioral changes of the CMS without and with antidepressant treatment were also tested using the forced swimming test [FST]. The results demonstrated the reversal of CMS-induced anhedonia after 3 weeks i.p. administration of 1 and 8 mg/kg/day paroxetine and venlafaxine, respectively. Furthermore, venlafaxine seems to be more efficacious than paroxetine in long-term behavioral changes recorded by the FST. Additionally, there was a significant [p<0.001] increase in the GABA content of the F.Cx of mice exposed to CMSinduced anhedonia. The present study suggested that GABA levels may be decreased in an animal model of depression and its reversal together with the behavior improvement by either paroxetine or venlafaxine could support the hypothesis that modification in GABAergic activity in mood disorders may complement the monoaminergic and serotonergic theories, proposing that the balance between multiple neurotransmitter systems may be altered in these disorders

Effect of moxonidine versus clonidine on stress induced gastric ulceration in rats

The present study was conducted to evaluate the effect of moxonidine a selective I imidazoline receptor agonist and antihypertensive agent versus clonidine on experimental gastric ulceration in rats. The animals were divided into 5 groups [10 animals each]. One served as control [stress ulcer induced] and received no medication. Two groups were pretreated intraperitoneally for 21 consecutive days with moxonidine [0.01 and 1 ing/kg b.w] respectively. The other 2 groups were pretreated intraperitoneally for 21 consecutive days with clonidine [0.01 and 1 mg/ kg b.w] respectively. Gastric ulceration in rats were induced by using restraint or immobilization technique. The animals were left for 24 hours and then the stomach was cut and examined for lesions to detect gastric ulceration. The effect of two doses of moxonidine and clonidine were tested on stress induced ulcer. Also, the effect of efaroxan [selective I - imidazoline receptor blocker] and yohimbine [selective a blacker] on the gastroprolective effect of moxonidine and clonidine were assessed respectively. The results of the present study revealed that stress ulcer incidence, severity and number per stomach were all higher in control group. Moxonidine [0.01 and 1 mg/kg] was found to exhibit a more pronounced gastroprotective effect on stress induced gastric ulcer compared to a- agonist clonidine <0.01 mg/ kg] with reduction of ulcer index by 59.5 and 79.6% for two doses of moxonidine respectively and 40.13% for clonidine in comparison to control group. However clonidine Img/kg decreased ulcer index by only 3.28%. The gastroprotective effect of moxonidine and low dose of clonidine were abolished following pretreatment with efaroxan and yohimbine respectively In conclusion, the results of the present study indicate that moxonidine exhibits a more pronounced gastroprotective effect compared to low dose of clonidine. In addition, the effects of clonidine on gastric function is dose dependent with no gastroprotective effect at higher doses. So, moxonidine may be considered a better alternative to clonidine as an anti-hypertensive in patients with gastrointestinal disorders