Behavioural pharmacology
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Behavioural pharmacology · Apr 2013
Comparative StudyThe effects of mGlu₇ receptor modulation in behavioural models sensitive to antidepressant action in two mouse strains.
There is increasing evidence suggesting a role of the neurotransmitter glutamate in depression. The metabotropic glutamate (mGlu) receptors are G-protein coupled receptors, which mediate a slow modulatory response to glutamate signalling. mGlu₇ receptor is a presynaptic inhibitory autoreceptor showing great promise as a potential therapeutic target for the treatment of depression. Selective pharmacological modulators of mGlu₇ receptor have been developed; the positive allosteric modulator AMN082 and the negative modulator 6-(4-methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo[4,5-c]pyridin-4(5H)-one hydrochloride (MMPIP). ⋯ Administration of MMPIP with AMN082 partially attenuated the antidepressant-like effect of AMN082 in C57BL/6j mice in the forced swim test and the TST. However, this effect was absent from the CD1 strain. This further adds to the growing corpus of data promoting the targeting of mGlu₇ receptor with the aim of achieving an antidepressant effect.
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Behavioural pharmacology · Apr 2013
Depressive-like behaviour induced by an intracerebroventricular injection of streptozotocin in mice: the protective effect of fluoxetine, antitumour necrosis factor-α and thalidomide therapies.
Information on the effect of an intracerebroventricular (i.c.v.) injection of streptozotocin (STZ) on noncognitive behaviour in rodents such as depression states is scarce. Thus, the aim of this study was to examine the depressive-like effect of STZ injected by the i.c.v. route in mice and the potential protective effect of fluoxetine, antitumour necrosis factor-α (anti-TNF-α) and thalidomide. Our results indicated that a single injection of STZ (0.1 mg/site) promoted depressive-like behaviour in the tail suspension and sucrose preference tests without altering either locomotor activity or plasma glucose levels. ⋯ This is the first study to report depressive-like effects of STZ using the i.c.v. route in mice. We concluded that fluoxetine, anti-TNF-α antibody and thalidomide were effective in preventing depressive-like behaviour and the increase in TNF-α levels in the hippocampus of mice induced by an i.c.v. injection of STZ, reinforcing the involvement of TNF-α in the pathophysiology of depression. This model and the mechanisms studied may contribute towards the development of new antidepressant drugs and enhance the options for studying depression.