Behavioral Depression and Positron Emission Tomography–Determined Serotonin 1A Receptor Binding Potential in Cynomolgus Monkeys

Abstract

This is the fourth in a series of studies that suggest that depressive behavior in adult female cynomolgus monkeys is similar to that observed in humans. It has been observed in 2 large groups of monkeys randomly selected from feral populations, suggesting that the capacity for depression is inherent in the species. This animal model holds promise to further our understanding of the basic mechanisms of affective behavior, the neuropathophysiologic characteristics of depression and the cognitive dysfunction that accompanies them, genetic and environmental factors that may affect depression risk, and the role of reproductive function in the excess depression risk in women.

Reduced 5-HT1A- and GABABReceptor Function in Dorsal Raphé Neurons Upon Chronic Fluoxetine Treatment of Socially Stressed Rats

“…These results appear in line with findings in monkeys that show symptoms of behavioral depression. In these animals, 5-HT 1A receptor binding at the level of the raphé nucleus (Shively et al 2006) were not affected.…”

Acute and chronic effects of citalopram on 5‐HT1A receptor—Labeling by [18F]MPPF and—Coupling to receptors‐G proteins

“…If we were to expect only a 20% decrease in [ (Maeda et al, 2001)] would have to be increased by 50-fold to produce an observable effect. In the mouse brain, the IC50 value of 5-HT was in the same range as in the rat brain, and pargyline at a dose inducing a 300-fold increase of 5-HT tissue content (Di Paolo et al, 1983) Haes et al, 2005;Zimmer et al, 2002a), whereas SSRIs like paroxetine (Jagoda et al, 2006) or citalopram (Ceglia et al, 2004) (Shively et al, 2006), and in patients with temporal lobe epilepsy (Merlet et al, 2004a,b) or Alzheimer disease (Kepe et al, 2006). Thus, long-term effects of chronic treatment with SSRIs upon 5-HT 1A receptor density should be detectable with this radioligand.…”

Increased Serotonin-1A (5-HT1A) Autoreceptor Expression and Reduced Raphe Serotonin Levels in Deformed Epidermal Autoregulatory Factor-1 (Deaf-1) Gene Knock-out Mice

“…Several studies report reduced 5-HT1A RNA or binding in the prefrontal cortex of subjects with major depression (24,(53)(54)(55)(56), consistent with reduced transcription of the 5-HT1A receptor. Similarly, in female cynomolgus monkeys, depressed status was associated with reduced 5-HT1A receptor levels in several forebrain regions (especially cingulate cortex, with lesser change in hippocampus and amygdala) with no change in the raphe region (57). In addition to the presence of the G(Ϫ1019) allele, reduction in Deaf-1 expression has also been associated with reduced 5-HT1A receptor expression in the prefrontal cortex of female depressed subjects (53).…”