Adaptive mechanisms following antidepressant drugs: Focus on serotonin 5-HT2A receptors.

BACKGROUND

There is a strong support for the role of serotonin (5-HT) neurotransmission in depression and in the mechanism of action of antidepressants. Among 5-HT receptors, 5-HT2A receptor subtype seems to be an important target implicated in the above disorder.

METHODS

The aim of the study was to investigate the effects of antidepressants, such as imipramine (15 mg/kg), escitalopram (10 mg/kg) and tianeptine (10 mg/kg) as well as drugs with antidepressant activity, including N-acetylcysteine (100 mg/kg) and URB597 (a fatty acid amide hydrolase inhibitor, 0.3 mg/kg) on the 5-HT2A receptor labeling pattern in selected rat brain regions. Following acute or chronic (14 days) drug administration, rat brains were analyzed by using autoradiography with the 5-HT2A receptor antagonist [3H]ketanserin.

RESULTS

Single dose or chronic administration of imipramine decreased the radioligand binding in the claustrum and cortical subregions. The [3H]ketanserin binding either increased or decreased in cortical areas after acute N-acetylcysteine and URB597 administration, respectively. A similar shift towards reduction of the [3H]ketanserin binding was detected in the nucleus accumbens shell following either acute treatment with imipramine, escitalopram, N-acetylcysteine and URB597 or repeated administration of imipramine, tianeptine and URB597.

CONCLUSIONS

In conclusion, the present result indicate different sensitivity of brain 5-HT2A receptors to antidepressant drugs depending on schedule of drug administration and rat brain regions. The decrease of accumbal shell 5-HT2A receptor labeling by antidepressant drugs exhibiting different primary mechanism of action seems to be a common targeting mechanism associated with the outcome of depression treatment.