Early postnatal allopregnanolone levels alteration and adult behavioral disruption in rats : Implication for drug abuse
Bartolomé Torrell, Iris (Universitat Autònoma de Barcelona. Institut de Neurociències)
Llidó, Anna (Universitat Autònoma de Barcelona. Institut de Neurociències)
Darbra Marges, Sònia (Universitat Autònoma de Barcelona. Institut de Neurociències)
Pallarès, Marc (Universitat Autònoma de Barcelona. Institut de Neurociències)

Data:	2019
Resum:	Several studies have highlighted the role that early postnatal levels of allopregnanolone play in the development of the CNS and adult behavior. Changes in allopregnanolone levels related to stress have been observed during early postnatal periods, and perinatal stress has been linked to neuropsychiatric disorders. The alteration of early postnatal allopregnanolone levels in the first weeks of life has been proven to affect adult behaviors, such as anxiety-related behaviors and the processing of sensory inputs. This review focuses on the first studies about the possible relationship between the early postnatal allopregnanolone levels and the vulnerability to abuse of drugs such as alcohol in adulthood, given that (1) changes in neonatal allopregnanolone levels affect novelty exploration and novelty seeking has been linked to vulnerability to drug abuse; (2) early postnatal administration of progesterone, the main allopregnanolone precursor, affects the maturation of dopaminergic meso-striatal systems, which have been related to novelty seeking and drug abuse; and (3) alcohol consumption increases plasma and brain allopregnanolone levels in animals and humans. Manipulating neonatal allopregnanolone by administering finasteride, an inhibitor of the 5α-reductase enzyme that participates in allopregnanolone synthesis, increases alcohol consumption and decreases the locomotor stimulant effects of low alcohol doses. At a molecular level, finasteride decreases dopamine and serotonin in ventral striatum and dopamine release in nucleus accumbens. Preliminary results suggest that serotonin 5HT3 receptors could also be affected. Although an in-depth study is necessary, evidence suggests that there is a relation between early postnatal allopregnanolone and vulnerability to drug use/abuse.
Ajuts:	Ministerio de Economía y Competitividad PSI2012-36646 Ministerio de Economía y Competitividad PSI2015-66582-P
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Emotional behavior ; Neurodevelopment ; Alcohol abuse ; Allopregnanolone ; Neurosteroids ; Neuropsychiatric disorders vulnerability
Publicat a:	Neurobiology of Stress, Vol. 12 (december 2019) , ISSN 2352-2895

DOI: 10.1016/j.ynstr.2019.100208
PMID: 32435661

13 p, 1.3 MB

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