Antidepressant activity models

While such models of depression are quite useful in conceptualizing the mechanisms behind antidepressant activity, they are assuredly an oversimplification of the actual pathophysiologic process of the disorder. Depression probably involves a complex dysregulation of monoamine systems, and these systems, in turn, modulate and are modulated by other neurobio-logic systems. Thus, the underlying cause of depression may well extend beyond dysfunction of the monoamine system.10... 

Muller WE, Rolli M, Schafer C, Hafner U. (1997). Effects of hypericum extract (LJ 160) in biochemical models of antidepressant activity. Pharmacopsychiatry. 30(suppl 2) 102-7. 

In humans, the antidepressant activity of NMDA receptor antagonists has not been evaluated extensively (Skohiick 1999). In animal models of depression, NMDA receptor antagonists have been reported to exert positive effects in most studies (Trullas 1997). This concerns mainly the forced swim test (Maj 1992 Moryl et al. 1993 PrzegaUnski et al. 1997) and stress-induced anhe-donia (Papp and Moryl 1994). Amantadine but not memantine was effective against reserpine-induced hypothermia (Moryl et al. 1993). In the forced swim test, both amino-adamantanes produced specific antidepressive-like activity (Moryl et al. 1993). 

Papp M, Moryl E (1994) Antidepressant activity of non-competitive and competitive NMDA receptor antagonists in a chronic mild stress model of depression. Em J Pharmacol 263 1-7... 

Luca Santarelli, Rene Hen, and their colleagues use a mouse model of depression and find evidence of a role of neurogenesis in antidepressant activity. 

Borsini F, Meli A Is the forced swimming test a suitable model for revealing antidepressant activity Psychopharmacology 94 147-160, 1988 Borsini F, Lecci A, Mancinelli A, et al Stimulation of dopamine D2 but not Dj receptors reduces immobility time of rats in the forced swimming test implication for antidepressant activity. Eur J Pharmacol 148 301-307, 1988 Bouchard JM, Delaunay J, Delisle J-P, et al Citalopram versus maprotiline a controlled clinical multicenter trial in depressed patients. Acta Psychiatr Scand 76 583-592, 1987... 

After the discovery of drugs with antidepressant activity in the late 1950s, an intensive search was undertaken for pharmacological models that would provide an understanding of the therapeutic effects observed and at the same time assist in the development of other, still more effective and specific antidepressants. In pharmacological tests then available, the prototype imipramine showed sedative, antihistaminic and anticholinergic effects and thus did not differ fundamentally from other medicaments with no antidepressant activity, e.g. antihistamines. The following observations then led to a further step forward in the development of hypotheses ... 

Opioid peptides have also been tested in animal models of depression and of antidepressant activity. Enkephalins and endorphins decreased immobility in the forced swim test and in the learned helplessness paradigm, demonstrating... 

Experiments and data presented in this chapter demonstrate that delta opioid agonists have antidepressant-like effects in animal models used to measure antidepressant activity. The antidepressant-like effects can be separated from other behavioral effects produced by these compounds, such as locomotor stimulation, convulsions, and learning impairments. This separation lends validity to this potential target for depression by eliminating effects or sources that may produce false positives. These compounds should be tested in other models of antidepressant activity to confirm these findings in the forced swim test. 

To further develop delta opioid receptor agonists as potential therapeutics, more compounds should be developed and evaluated in the forced swim test and other models of antidepressant activity. This may allow for the identification of delta opioid agonists with even more selective behavioral effects. Indeed, there are a number of delta opioid agonists with different basic chemical structures that may prove useful. 

The most researched area of interest for antidepressant activity related to signaling pathways is the hippocampus (79-85). The volume of the hippocampus is reduced in patients with multiple episodes of major depression, as observed in imaging studies and in postmortem samples (81-84). Animal models of inescapable stress are associated with decreased hippocampal neurogenesis (84). Neurogenesis is also evident in the hippocampus of humans (85). The neurogenesis hypothesis of depression states that depression is a consequence of impaired... 

Cryan JE, Mombereau C, Vassout A (2005b) The tail suspension test as a model for assessing antidepressant activity Review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev 29 571-625. 

Jensen AG, Hansen SH, Nielsen EO. Adhyperforin as a contributor to the effect of Hypericum perforatum L. in biochemical models of antidepressant activity. Life Sci 2001 68 1593-1605. 

In contrast, bupropion metabolites, showed various degrees of activity in several animal models of antidepressant activity... 

Other mixed 5HT-1A agonist/5HT-2 antagonist that shows anxiolytic, as well as antidepressant, activity in preclinical models (483). The development of adatanserin and HT-90B has been discontinued. 

Sairam K, Dorababu M, Goel RK, Bhattacharya SK (2002) Antidepressant activity of standardized extract of Bacopa monniera in experimental models of depression in rats. Phytomedicine 9 207-211... 

Monoamine oxidase amperometric biosensor based on SPE were also modified with MWCNT by using the drop casting technique for the determination of antidepressants in model solutions and dosage forms. The authors used BSA protein which provided a matrix for the immobilization of the enzyme and protection of the enzyme activity when glutaraldehyde is used as a linker. Serafin et aZ. developed a label free dual immunosensor for the determination of human growth and prolactin hormones. The electrochemical immunosensor was based on CNT modify carbon SPE platform with the presence of poly(ethylene-dioxythiophene) (PEDOT) and gold nanoparticles. Again, the hybrid nano-material composite facilitated a proper immobilization of the antibody on the electrode matrix. 

Antidepressant activity. In two different studies, Pan et al. demonstrated that icariin, isolated from E. brevicornum, had an antide-pressant-like effect in the forced swimming test and tail suspension test in mice after oral administration for 21 and 7 days, respectively. The 21-day treatment also resulted in a decrease in the levels of MAO and serum CRF. Further investigation of its mechanism of action in rats showed that icariin reduced the serum levels of CRF, IL-6, and TNF-a resulting in the chronic mild stress model utilized in the study. ... 

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