Effect of pindolol on serotonin response in dorsal raphe nucleus neurons in mice brain

Antidepressants are effective in treatment of mood disorders like major depression. However, in the first few days of their usage, they lead to increase in serotonin level in the somatodendritic region of the serotonergic dorsal raphe nucleus (DRN) neurons, inhibiting the serotonergic neurons locally. Pindolol may eliminate this inhibition when used in combination with antidepressants. In this research, Balb/c mice, 28-34 days-old, were used. Electrophysiological recordings from the neurons in the dorsal subnucleus of the dorsal raphe were obtained by using the patch clamp technique. Serotonin application (25µM) resulted in 14.3 ± 3.14 mV (n = 9) hyperpolarization (p˂0.05) of resting membrane potential and induced an outward current by 23.36 ± 3.79 pA (n = 27). This effect was inhibited by pre-administration of quinine (GIRK blocker, 1mM), WAY-100135 (5-HT1A blocker, 21 µM) and pindolol (10µM) separately. (P˂0.05). 8-OHDPAT (5-HT1A agonist, 30µM) induced a serotonin-like outward flow (p˃0.05), which was inhibited by pre-administration of pindolol (10µM) (p˂0.05). Besides, combination of venlafaxine (20 mg/kg/day) and pindolol (15 mg/kg/day) significantly reduced immobilization time compared to the control group in tail suspension test and forced swimming test (p<0.05) without any change in locomotor activity. Venlafaxine or pindolol alone did not significantly reduce immobilization time (p>0.05). In conclusion, pindolol, which blocks somatodendritic 5-HT1A receptors, has the potential to prevent the inhibition of serotonergic neurons resulting from increased serotonin levels in the DRN after antidepressant use. Hence, pindolol can potentiate antidepressant effect of venlafaxine. In the mood disorders that do not respond to antidepressant treatment, pindolol is likely to increase the effectiveness of antidepressant drugs when given in combination.