A new model for the detection of antidepressant drugs: Olfactory bulbectomy in the rat compared with existing models

Cairncross, K.D.; Cox, B.; Förster, Christine; Wren, A.

doi:10.1016/0160-5402(78)90018-9

Cited by 80 publications

(20 citation statements)

References 7 publications

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“…Consequently, the OBX syndrome is believed to result from dysfunction in brainstem and limbic areas involving a variety of neurochemical and neuropharmacological changes affecting many different transmitter systems (Pohorecky et al 1969;Hirsh 1980;Janscar and Leonard 1984;Tiong and Richardson 1990;Gurevich et al 1993). Numerous studies have also demonstrated that many of the behavioral and biochemical alterations invoked by OBX are reversed by chronic administration of most antidepressant drugs (Van Riezen et al 1976;Cairncross et al 1978Cairncross et al , 1979aJesberger and Richardson 1986;Kelly et al 1997).…”

Section: Introductionmentioning

confidence: 96%

Antidepressants preferentially enhance habituation to novelty in the olfactory bulbectomized rat

2000

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Section: Introductionmentioning

confidence: 96%

Antidepressants preferentially enhance habituation to novelty in the olfactory bulbectomized rat

2000

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“…Since the amygdala plays an important role in passive avoidance behaviour [ 131, a relation between the reduced noradrenergic metabolism in this area and deficits in passive avoidance behaviour of olfactory bulbectomized rats [2, 15, 161 is possible. Interesting in this respect is the fact that clinically active antidepressants like the tricyclics and like Mianserin are able to normalize this deficit in passive avoidance behaviour [2]. In previous experiments (unpublished) we were unable to observe consistent effects of antidepressants on NE levels in the amygdaloid cortex of olfactory bulbectomized rats.…”

Section: Discussionmentioning

confidence: 79%

Changes in rat brain norepinephrine levels and turnover after olfactory bulbectomy

Tonnaer¹,

Rigter²,

Versteeg³

et al. 1980

Brain Research Bulletin

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. NICKOLSON. Changes in rat bruin norepinephrine levels and turnover after olfactory hulbectomy. BRAIN RES. BULL. 5(6) [683][684][685][686] 1980.-After bilateral olfactory bulbectomy in rats a significant increase of norepinephrine (NE) level in the hypothalamus was found. However, no difference was observed between hypothalamic NE turnover of bulbectomized and sham operated animals. In the amygdaloid cortex the NE level was not affected by bulbectomy. In this area, however, the NE turnover appeared to be decreased after bulbectomy. The latter finding may be related to the deficits in passive avoidance behaviour as found in bulbectomized rats. Olfactory bulbectomyNorepinephrine Hypothalamus Amygdaloid cortex VARIOUS attempts have been made to develop new animal models for the detection of potential antidepressants.One of the models which has been studied rather extensively is the olfactory bulbectomized rat. After bulbectomy in rats, behavioural variables such as passive avoidance behaviour are changed and these changes are generally reversed by antidepressant drugs [2, 15, 161. In preliminary experiments, the effects of bulbectomy on neurotransmitter levels in various brain areas were studied. Since the most prominent bulbectomy-induced change was found in hypothalamic NE levels (unpublished results), the present experiments were done to determine the levels and turnover of NE in rat hypothalamus. In addition, NE levels and turnover in rat amygdaloid cortex were studied because this part of the limbic system is closely connected to the olfactory bulb [ 1, 10, 1 l] and may play an important role in passive avoidance behaviour [13]. METHOD Animals and OperationMale Wistar (WU-Cpb) rats of about 200 g were anaesthetized with 3% tribromoethanol (Avertine), 1.1 ml/l00 g bodyweight IP. The animal's head was fixed in a stereotaxic frame. A midline incision in the skin and periosteum was made. The skin and periosteum were retracted, the skull cleaned and a hole (1.5 mm4) was drilled by hand in the skull on the midline, 2 mm frontal to bregma. The olfactory bulbs were cut off with a sharpened needle, just rostra1 to the frontal lobe, and removed by aspiration. The hole was closed by Spongostan Dental, the wound desinfected by Exoseptolix woundpowder and the skin sutured by two agraves.Sham operations were performed by almost perforating the skull, the skull and dura were then perforated carefully with a needle, so that bleeding arose beneath the skull.Not more than six animals were housed in a cage and the experimental animals were separated from the sham operated controls.Experimental Design NE levels. Twenty-eight days after surgery the animals were decapitated, the brains dissected and the NE concentrations measured in the hypothalamus and amygdaloid cortex. Decapitation, dissection and extraction of NE were carried out following a randomized block design or a completely randomized design, and NE estimated using a fluorimetric respective radiochemical method.NE concentrations of bulbectomized animals were averaged,...

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“…A more selective model of depression such as hypermotility in olfactory bulbectomised rats 26 , model of chronic mild stress may be chosen in future studies to validate the antidepressant effect of piracetam.…”

Section: Resultsmentioning

confidence: 99%

Untitled

2013

IJPSR

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ABSTRACT:Aims: To study effect of piracetam in experimental models of depression. Methods: Mice (n = 6/group) pretreated with distilled water, fluoxetine (28 mg/kg) and piracetam -100, 200, 300, 400, 500, 750 and 1000 mg/kg for 7 days were subjected to tail suspension test (TST) on day 7. Rats (n=6/group) were pretreated for 7 days with distilled water, fluoxetine (20 mg/kg) and piracetam (300, 400, 500, 750 and 1000 mg/kg) and on day 7, forced swim test (FST) was conducted. Immobility time in seconds was noted in both the models and analysed using oneway ANOVA (level of significance p<0.05). Results: In TST, immobility time was reduced significantly (p<0.01) and in a dose-dependent manner with all but one dose of piracetam compared to vehicle. In FST, significant difference from control group was seen with higher doses of piracetam (500, 750 and 1000 mg/kg) with a dose-dependent trend. The mean immobility durations in the groups with significant improvement were found to be comparable to that of the respective fluoxetine groups in both models. No signifiant difference was seen in the general motor activity in all the treatment groups as assessed by the open field test. Conclusion: Piracetam shows anti-depressant activity in experimental models of depression over a wide dose range and in a dose-dependent manner.

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A new model for the detection of antidepressant drugs: Olfactory bulbectomy in the rat compared with existing models

Cited by 80 publications

References 7 publications

Antidepressants preferentially enhance habituation to novelty in the olfactory bulbectomized rat

Antidepressants preferentially enhance habituation to novelty in the olfactory bulbectomized rat

Changes in rat brain norepinephrine levels and turnover after olfactory bulbectomy

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