Evidence of the activity of lithium on 5-HT1B receptors in the mouse forced swimming test: comparison with carbamazepine and sodium valproate

The use of lithium in combination with various antidepressant drugs (e.g., heterocyclics and monoamine oxidase inhibitors) has been reported rapidly t o improve antidepressant response in otherwise treatment-resistant patients . Carbamazepine and sodium valproate have also been shown to be effective i n the treatment of several forms of affective disorders, such as treatment- resistant depression and bipolar depression. The present study, using the m ouse forced swimming test, was undertaken to test the hypothesis of the act ion of lithium, carbamazepine or sodium valproate on some 5-HT receptor sub types. Results showed that lithium significantly potentiated the anti-immob ility effects of RU 24969 (P < 0.01) and anpirtoline (P < 0.01). Pretreatme nt with lithium did not induce any significant antidepressant-like effects when tested in combination with 8-OH-DPAT, NAN-190 or (+/-) pindolol. Pretr eatment with carbamazepine provoked anti-immobility effects when tested in combination with RU 24969 (P < 0.01) and 8-OH-DPAT (P < 0.01), whereas prio r administration of sodium valproate enhanced the antidepressant-like effec ts of (+/-) pindolol (P < 0.01), 8-OH-DPAT (P < 0.01) and RU 24969 (P < 0.0 1). In conclusion, the results of the present study suggest that lithium ma y be acting through 5-HT1B receptors, whereas the action of carbamazepine a nd sodium valproate seems to involve 5-HT1A receptors in the mouse forced s wimming test. However, considering the complexity of the actions of these c ompounds, it is possible that other neurotransmitter systems/receptors may be involved.