Pindolol excites dopaminergic and adrenergic neurons, and inhibits serotonergic neurons, by activation of 5-HT1A receptors

Pindolol accelerates the clinical actions of selective serotonin reuptake i nhibitors (SSRIs) in man, and modulates extracellular levels of monoamines in corticolimbic structures in rats. Herein, we examined its influence upon electrical activity of serotonergic, dopaminergic and adrenergic perikarya in the dorsal raphe nucleus (DRN), ventral tegmental area (VTA) and locus coeruleus (LC) of anaesthetized rats. In analogy to the serotonin(1A), (5-H T1A) agonist, 8-OH-DPAT (-100%), pindolol dose-dependently (0.063-1.0 mg/kg ) decreased (-70%) the firing rate of serotonergic neurons. The inhibitory action of pindolol was abolished by the selective 5-HT1A antagonist, WAY-10 0,635 (0.031 mg/kg). In contrast, 8-OH-DPAT (+26%) and pindolol (0.25-4.0 m g/kg, +60%) dose-dependently increased the firing rate of dopaminergic cell s. Of 57 neurons recorded (pindolol, 2.0 mg/kg), 36 (63%) were excited, 11 (19%) were unaffected and 10 (18%) were inhibited. This variable influence could be attributed to regularly firing neurons in the parabrachial subdivi sion, inasmuch as all neurons in the paranigral subnucleus were excited. Th e facilitation of firing by pindolol was accompanied by an increase in burs t firing throughout the VTA. Both the increases in burst firing and in firi ng rate were reversed by WAY-100,635 (0.031 mg/kg). Finally, the electrical activity of adrenergic neurons was dose-dependently enhanced by 8-OH-DPAT and pindolol (+99% and +83%, respectively). WAY-100,635 reversed this excit ation and, itself, inhibited the activity of adrenergic neurons. In conclus ion, via engagement of 5-HT1A receptors, pindolol inhibits serotonergic, an d activates dopaminergic and adrenergic, neurons in anaesthetized rats. Suc h actions may contribute to its influence upon mood, both alone and in asso ciation with antidepressant agents.