Effects of Subchronic Buspirone Treatment on Depressive Profile in Socially Isolated Rats: Implication of Early Life Experience on 5-HT1A Receptor-Related Depression

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2024 Jun 27

PMID 38931384

Authors

Nian-Sheng Tzeng

Jing-Yi Chung

Chen-Cheng Lin

Pao-Yun Cheng

Yia-Ping Liu

Affiliations

Soon will be listed here.

Abstract

The heterogeneity of etiology may serve as a crucial factor in the challenges of treatment, including the low response rate and the delay in establishing therapeutic effect. In the present study, we examined whether social experience since early life is one of the etiologies, with the involvement of the 5-HT1A receptors, and explored the potentially therapeutic action of the subchronic administration of buspirone, a partial 5-HT1A agonist. Rats were isolation reared (IR) since their weaning, and the depressive profile indexed by the forced-swim test (FST) was examined in adulthood. Nonspecific locomotor activity was used for the IR validation. Buspirone administration (1 mg/kg/day) was introduced for 14 days (week 9-11). The immobility score of the FST was examined before and after the buspirone administration. Tissue levels of serotonin (5-HT) and its metabolite 5-HIAA were measured in the hippocampus, the amygdala, and the prefrontal cortex. Efflux levels of 5-HT, dopamine (DA), and norepinephrine (NE) were detected in the hippocampus by brain dialysis. Finally, the full 5-HT1A agonist 8-OH-DPAT (0.5 mg/kg) was acutely administered in both behavioral testing and the dialysis experiment. Our results showed (i) increased immobility time in the FST for the IR rats as compared to the social controls, which could not be reversed by the buspirone administration; (ii) IR-induced FST immobility in rats receiving buspirone was corrected by the 8-OH-DPAT; and (iii) IR-induced reduction in hippocampal 5-HT levels can be reversed by the buspirone administration. Our data indicated the 5-HT1A receptor-linked early life social experience as one of the mechanisms of later life depressive mood.

References

Celada P, Bortolozzi A, Artigas F . Serotonin 5-HT1A receptors as targets for agents to treat psychiatric disorders: rationale and current status of research. CNS Drugs. 2013; 27(9):703-16. DOI: 10.1007/s40263-013-0071-0. View

Tung C, Lin Y, Lin C, Liu Y . Time-Dependent Effects of Buspirone versus Desipramine on the 5-Choice Serial Reaction Time Task in Rats Reared in Social Isolation: Implication of Early Life Experience and Motoric Impulsivity. J Integr Neurosci. 2023; 22(4):80. DOI: 10.31083/j.jin2204080. View

Aswar U, Shende H, Aswar M . Buspirone, a 5-HT1A agonist attenuates social isolation-induced behavior deficits in rats: a comparative study with fluoxetine. Behav Pharmacol. 2022; 33(5):309-321. DOI: 10.1097/FBP.0000000000000679. View

Jaronczyk M, Chilmonczyk Z, Mazurek A, Nowak G, Ravna A, Kristiansen K . The molecular interactions of buspirone analogues with the serotonin transporter. Bioorg Med Chem. 2008; 16(20):9283-94. DOI: 10.1016/j.bmc.2008.09.005. View

Carver C, Johnson S, Joormann J, Kim Y, Nam J . Serotonin transporter polymorphism interacts with childhood adversity to predict aspects of impulsivity. Psychol Sci. 2011; 22(5):589-95. DOI: 10.1177/0956797611404085. View

Sato H, Skelin I, Diksic M . Chronic buspirone treatment decreases 5-HT1B receptor densities and the serotonin transporter but increases the density of 5-HT2A receptors in the bulbectomized rat model of depression: an autoradiographic study. Brain Res. 2010; 1345:28-44. DOI: 10.1016/j.brainres.2010.05.054. View

Hjorth S, Carlsson A . Buspirone: effects on central monoaminergic transmission--possible relevance to animal experimental and clinical findings. Eur J Pharmacol. 1982; 83(3-4):299-303. DOI: 10.1016/0014-2999(82)90265-5. View

Lalonde R, Strazielle C . Regional variations of 5HT concentrations in Rorasg (staggerer) mutants. Neurochem Res. 2006; 31(7):921-4. DOI: 10.1007/s11064-006-9096-9. View

McCormick C, Green M . From the stressed adolescent to the anxious and depressed adult: investigations in rodent models. Neuroscience. 2012; 249:242-57. DOI: 10.1016/j.neuroscience.2012.08.063. View

10.

Koenen K, Moffitt T, Poulton R, Martin J, Caspi A . Early childhood factors associated with the development of post-traumatic stress disorder: results from a longitudinal birth cohort. Psychol Med. 2006; 37(2):181-92. PMC: 2254221. DOI: 10.1017/S0033291706009019. View

11.

Frances H, Lienard C . Isolation-induced social behavioral deficit test: effect of tranquilizing drugs. Pharmacol Biochem Behav. 1989; 34(2):293-6. DOI: 10.1016/0091-3057(89)90314-6. View

12.

Blier P, Ward N . Is there a role for 5-HT1A agonists in the treatment of depression?. Biol Psychiatry. 2003; 53(3):193-203. DOI: 10.1016/s0006-3223(02)01643-8. View

13.

Sprouse J, Aghajanian G . Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B agonists: a comparative study with dorsal raphe neurons. Neuropharmacology. 1988; 27(7):707-15. DOI: 10.1016/0028-3908(88)90079-2. View

14.

Kokras N, Pastromas N, Papasava D, de Bournonville C, Cornil C, Dalla C . Sex differences in behavioral and neurochemical effects of gonadectomy and aromatase inhibition in rats. Psychoneuroendocrinology. 2017; 87:93-107. DOI: 10.1016/j.psyneuen.2017.10.007. View

15.

Dimonte S, Sikora V, Bove M, Morgese M, Tucci P, Schiavone S . Social isolation from early life induces anxiety-like behaviors in adult rats: Relation to neuroendocrine and neurochemical dysfunctions. Biomed Pharmacother. 2023; 158:114181. DOI: 10.1016/j.biopha.2022.114181. View

16.

Sikich L, Hickok J, Todd R . 5-HT1A receptors control neurite branching during development. Brain Res Dev Brain Res. 1990; 56(2):269-74. DOI: 10.1016/0165-3806(90)90092-d. View

17.

Chekroud A, Gueorguieva R, Krumholz H, Trivedi M, Krystal J, McCarthy G . Reevaluating the Efficacy and Predictability of Antidepressant Treatments: A Symptom Clustering Approach. JAMA Psychiatry. 2017; 74(4):370-378. PMC: 5863470. DOI: 10.1001/jamapsychiatry.2017.0025. View

18.

Bergmann B, Seiden L, Landis C, Gilliland M, Rechtschaffen A . Sleep deprivation in the rat: XVIII. Regional brain levels of monoamines and their metabolites. Sleep. 1994; 17(7):583-9. DOI: 10.1093/sleep/17.7.583. View

19.

Lea J, Stoner S, Lafollette J . Agitation associated with aripiprazole initiation. Pharmacotherapy. 2007; 27(9):1339-42. DOI: 10.1592/phco.27.9.1339. View

20.

Zhou F, Hobin J, BORELLA A . Isolation-rearing of rats produces deficits as adults in the serotonergic innervation of hippocampus. Peptides. 2000; 21(11):1755-9. DOI: 10.1016/s0196-9781(00)00327-2. View