Selective serotonin reuptake inhibitors (SSRIs), such as citalopram (CTM), have 
been widely prescribed for major depressive disorder, not only for adult 
populations, but also for children and pregnant mothers. Recent evidence 
suggests that chronic SSRI exposure in adults increases serotonin (5-HT) levels 
in the raphe system and decreases norepinephrine (NE) locus ceruleus (LC) neural 
activity, suggesting a robust opposing interaction between these two monoamines. 
In contrast, perinatal SSRI exposure induces a long-lasting downregulation of 
the 5-HT-raphe system, which is opposite to that seen with chronic adult 
treatment. Therefore, the goal of the present investigation was to test the 
hypothesis that perinatal CTM exposure (20 mg/kg/d) from postnatal day 1 (PN1) 
to PN10 leads to hyperexcited NE-LC circuit function in adult rats (>PN90). Our 
single-neuron LC electrophysiological data demonstrated an increase in 
spontaneous and stimulus-driven neural activity, including an increase in phasic 
bursts in CTM-exposed animals. In addition, we demonstrated a corresponding 
immunoreactive increase in the rate-limiting catalyzing catecholamine enzyme 
(tyrosine hydroxylase) within the LC and their neocortical target sites compared 
to saline controls. Moreover, these effects were only evident in male exposed 
rats, suggesting a sexual dimorphism in neural development after SSRI exposure. 
Together, these results indicate that administration of SSRIs during a sensitive 
period of brain development results in long-lasting alterations in NE-LC circuit 
function in adults and may be useful in understanding the etiology of pervasive 
developmental disorders such as autism spectrum disorder.