The effect of venlafaxine treatment on the behavioural and neurochemical changes in the olfactory bulbectomised rat

Abstract

In the present study, the effect of chronic treatment with venlafaxine on beta1 and 5-HT2 receptor populations was examined in the frontal cortex of olfactory bulbectomised (OB) and sham operated (SO) animals. The effect of these drugs on the behaviour of the animals on the elevated plus maze and the "open field" was also assessed. Removal of the bulbs resulted in a characteristic increase in locomotor activity in the OB animals in the "open field" which was reversed by chronic venlafaxine treatment. Venlafaxine produced a slight reduction in the number of open arm entries made by the OB animals although this failed to reach significance. Maximum change in temperature from baseline, following a single dose of 8-OH-DPAT (1.5 mg kg(-1) SC), was used to assess the function of the 5-HT1A receptors. Chronic venlafaxine treatment had no effect on the hypothermic response to 8-OH-DPAT in the present study. A decrease in the affinity of beta1-adrenoceptors was found following olfactory bulbectomy and this was normalised by treatment with venlafaxine. No bulbectomy-induced changes were evident 32 days post surgery in beta1-adrenoceptor density; however, chronic treatment with venlafaxine significantly reduced the density of these receptors in the OB animals. Olfactory bulbectomy did not produce any changes in 5-HT2 receptor populations but venlafaxine administration significantly reduced the density of these receptors in both SO and OB animals. The findings of the present study further validate the usefulness of the OB as an animal model, for the detection of antidepressants from a wide variety of classes.

Effects of milnacipran and fluvoxamine on hyperemotional behaviors and the loss of tryptophan hydroxylase-positive cells in olfactory bulbectomized rats

“…Contrary to our results, Wieronska et al (2001) reported that OBX rats produced the decreased level of anxiety in the elevated plus maze. Furthermore, it was reported that subchronic treatment with SNRIs venlafaxine reversed the OBX-induced hyperactivity in the open field apparatus, whereas there are no significant effects on the performance in the elevated plus maze (McGrath and Norman 1998). However, we found that milnacipran reversed the performance in the elevated plus maze as well as hyperemotional score in OBX rats.…”

Dose-Related Effects of Chronic Antidepressants on Neuroprotective Proteins BDNF, Bcl-2 and Cu/Zn-SOD in Rat Hippocampus

“…Neither were abnormalities found in the animals' general health or demeanor. In fact, the doses used in the present study have been demonstrated to be effective in animal models (Stockert et al, 1988;Bodnoff et al, 1989;Malatynska et al, 1995;Ferretti et al, 1995;McGrath and Norman 1998;Gur et al, 2002). Although we have not yet determined the causative factors for this paradox, the dose-related effects of the drugs on the BDNF immunostaining in hippocampal neurons may have functional significance and should be explored further.…”

Pharmacological Blockade of 5-HT7 Receptors as a Putative Fast Acting Antidepressant Strategy

“…It is therefore difficult to determine if SB-269970 has a more rapid onset of action in comparison with these ADs based on this test. To address this issue, we used OBX rats, which require long-term (2-3 weeks) treatment to observe an AD-like response (McGrath and Norman, 1998;Song and Leonard, 2005). An exaggeration of locomotor activity in OBX animals was observed compared with sham rats when placed in a high illuminated open-field ( Figure 6).…”