Increased dopamine D 2 /D 3 receptor and serotonin transporter availability in male rats after spontaneous remission from repeated social defeat-induced depression; a PET study in rats

• Published in: Neurobiology of disease 2024-11, Vol.202, p.106727
• Main Authors: Moraga-Amaro, Rodrigo, Vazquez-Matias, Daniel Aaron, Nazario, Luiza Reali, Dierckx, Rudi A J O, Stehberg, Jimmy, Doorduin, Janine, de Vries, Erik F J
• Format: Article
• Language: English
• Subjects: Animals; Brain - diagnostic imaging; Brain - metabolism; Depression - metabolism; Disease Models, Animal; Male; Positron-Emission Tomography - methods; Rats; Rats, Wistar; Receptors, Dopamine D2 - metabolism; Receptors, Dopamine D3 - metabolism; Remission, Spontaneous; Serotonin Plasma Membrane Transport Proteins - metabolism; Social Defeat
• ISSN: 1095-953X

Most pharmacological treatments for depression target monoamine transporters and about 50 % of treated patients attain symptomatic remission. Once remission is attained, it is hard to distinguish the changes on brain monoaminergic transmission induced by the antidepressants, from those associated to remission per se. In this study, we aimed at studying the brain of spontaneously remitted rats from repeated social defeat (RSD)-induced depression in terms of dopamine D /D receptor and serotonin transporter (SERT) availability, showing absence of depressive symptoms 2 weeks after RSD. We combined behavioral tests and positron emission tomography (PET) with [ C]raclopride and [ C]DASB to explore the changes in dopamine D /D receptor and serotonin transporter (SERT) availability, respectively. Male rats submitted to RSD showed increased peripheral corticosterone levels, decreased body weight and anhedonia, as measured with the sucrose preference test, 1 day after RSD, confirming depressive-like symptoms. These depressive-like symptoms were no longer present 2 weeks after RSD. Rats that recovered from depressive-like symptoms showed decreased D /D receptor binding in the caudate putamen and increased SERT availability in the brainstem, insular cortex, midbrain and thalamus, compared to control non-stressed animals. Our study shows that remission of depressive-like symptoms does not just "normalize" monoaminergic transmission, as changes in dopaminergic and serotonergic neurotransmission linger in several brain regions even after depressive-like symptoms have already resolved. These results provide new insights into the brain changes associated to remission in the RSD-induced depression model in rats.