Effects of prenatal exposure to fluoxetine on circadian rhythmicity in the locomotor activity and neuropeptide Y and 5‐HT expression in male and female adult Wistar rats

Abstract

Serotonin (5-HT) reuptake inhibitors, such as fluoxetine, are the most prescribed antidepressant for maternal depression. In this sense, it exposes mothers and the brains of infants to increased modulatory and trophic effects of serotonergic neurotransmission. 5-HT promotes essential brain changes throughout its development, which include neuron migration, differentiation and organisation of neural circuitries related to emotional, cognitive and circadian behavior. Early exposure to the SSRIs induces long-term effects on behavioral and neural serotonergic signalisation. We have aimed to evaluate the circadian rhythm of locomotor activity and the neurochemical content, neuropeptide Y (NPY) and 5-HT in three brain areas: intergeniculate leaflet (IGL), suprachiasmatic nuclei (SCN) and raphe nuclei (RN), at two zeitgebers (ZT6 and ZT18), in male and female rat's offspring early exposed (developmental period GD13-GD21) to fluoxetine (20 mg/kg). First, we have conducted daily records of the locomotor activity rhythm using activity sensors coupled to individual cages over 4 weeks. We have lastly evaluated the immunoreactivity of NPY in both SCN and IGL, as well the 5-HT expression in the dorsal and medial RN. In summary, our results showed that (1) prenatal fluoxetine affects phase entrainment of the rest/activity rhythm at ZT6 and ZT18, more in male than female specimens, and (2) modulates the NPY and 5-HT expression. Here, we show male rats are more susceptible to phase entrainment and the NPY and 5-HT misexpression compared to female ones. The sex differences induced by early exposure to fluoxetine in both the circadian rhythm of locomotor activity and the neurochemical expression into SCN, IGL and midbrain

Putative identification of proopiomelanocortin and neuropeptide-Y neurons of the arcuate nucleus by their response to leptin: in vivo electrophysiology study in male and female rats

“…Interestingly, previous studies reported no sex differences in the brain NPY mRNA (Hill et al 2014) or protein (Henn et al 2021;Carboni et al 2022;Linhares et al 2022) levels. With regards to the specific receptors mediating NPY transmission, the density of the cortical NPY receptors Y1 was higher in males, while their affinity was greater in females (Michel et al 1995).…”

Blue light exposure-dependent improvement in robustness of circadian rest-activity rhythm in aged rats

“…However, as the rest-activity rhythm does not perform like a cosine function [ 62 ], other non-parametric variables were needed as IS, IV, L5, and M10 to see locomotor activity in detail [ 60 ]. Although M10 and L5 are based on rest-activity rhythm in humans, the use of these parameters in animals has been described in the literature in rats [ 68 ], mice [ 69 ], and marmosets [ 70 , 71 ].…”