Effects of chronic citalopram treatment on 5-HT1A and 5-HT2A receptors in group- and isolation-housed mice

Selective serotonin reuptake inhibitors (SSRI) are characterized by high clinical effectiveness and good tolerability. A 2–3 week delay in the onset of effects is caused by adaptive mechanisms, probably at the serotonergic (5-HT) receptor level. To analyze this in detail, we measured 5-HT1A and 5-HT2A receptor bindings in vitro after 3 weeks of citalopram treatment (20 mg/kg i.p. daily) in group-housed as well as isolation-housed mice, reflecting neurobiological aspects seen in psychiatric patients.Isolation housing increased somatodendritic (+ 52%) and postsynaptic (+ 30–95%) 5-HT1A as well as postsynaptic 5-HT2A receptor binding (+ 25–34%), which confirms previous findings. Chronic citalopram treatment did not induce alterations in raphe 5-HT1A autoreceptor binding, independent of housing conditions. Housing-dependent citalopram effects on postsynaptic 5-HT1A receptor binding were found with increases in group- (+ 11–42%) but decreases in isolation-housed (− 11 to 35%) mice. Forebrain 5-HT2A receptor binding decreased between 11 and 38% after chronic citalopram administration, independent of housing conditions. Citalopram's long-term action comprises alterations at the postsynaptic 5-HT1A and 5-HT2A receptor binding levels. Housing conditions interact with citalopram effects, especially on 5-HT1A receptor binding, and should be more strongly considered in pharmacological studies. In general, SSRI-induced alterations were more pronounced and affected more brain regions in isolates, supporting the concept of a higher responsiveness in “stressed” animals. Isolation-induced receptor binding changes were partly normalized by chronic citalopram treatment, suggesting the isolation housing model for further analyses of SSRI effects, especially at the behavioral level.