Serotonin is a common thread linking different classes of antidepressants.

Depression pathology remains elusive. The monoamine hypothesis has placed much focus on serotonin, but due to the variable clinical efficacy of monoamine reuptake inhibitors, the community is looking for alternative therapies such as ketamine (neurogenesis theory of antidepressant action). There is evidence that different classes of antidepressants may affect serotonin levels; a notion we test here. We measure hippocampal serotonin in mice with voltammetry and study the effects of acute challenges of escitalopram, fluoxetine, reboxetine, and ketamine. We find that pseudo-equivalent doses of these drugs similarly raise ambient serotonin levels, despite their differing pharmacodynamics because of differences in Uptake 1 and 2, rapid SERT trafficking, and modulation of serotonin by histamine. These antidepressants have different pharmacodynamics but have strikingly similar effects on extracellular serotonin. Our findings suggest that serotonin is a common thread that links clinically effective antidepressants, synergizing different theories of depression (synaptic plasticity, neurogenesis, and the monoamine hypothesis).

Selective monoaminergic and histaminergic circuit dysregulation following long-term HIV-1 protein exposure.

Between 30 and 60% of HIV-seropositive individuals develop symptoms of clinical depression and/or apathy. Dopamine and serotonin are associated with motivational alterations; however, histamine is less well studied. In the present study, we used fast-scan cyclic voltammetry in HIV-1 transgenic (Tg) rats to simultaneously analyze the kinetics of nucleus accumbens dopamine (DA), prefrontal cortical serotonin (5-HT), and hypothalamic histamine (HA). For voltammetry, subjects were 15 HIV-1 Tg (7 male, 8 female) and 20 F344/N (11 male, 9 female) adult rats. Both serotonergic and dopaminergic release and reuptake kinetics were decreased in HIV-1 Tg animals relative to controls. In contrast, rates of histamine release and reuptake increased in HIV-1 Tg rats. Additionally, we used immunohistochemical (IHC) methods to identify histaminergic neurons in the tuberomammillary nucleus (TMN) of the hypothalamus. For IHC, subjects were 9 HIV-1 Tg (5 male, 4 female) and 9 F344/N (5 male, 4 female) adult rats. Although the total number of TMN histaminergic cells did not differ between HIV-1 Tg rats and F344/N controls, a significant sex effect was found, with females having an increased number of histaminergic neurons, relative to males. Collectively, these findings illustrate neurochemical alterations that potentially underlie or exacerbate the pathogenesis of clinical depression and/or apathy in HIV-1.