Altered nocifensive behavior in animal models of autism spectrum disorder: The role of the nicotinic cholinergic system

NEUROPHARMACOLOGY

卷:111

Article

Wang, Li¹  Almeida, Luis E. F.¹  Nettleton, Margaret¹  Khaibullina, Alfia¹  Albani, Sarah¹  Kamimura, Sayuri¹  Nouraie, Mehdi.²  Quezado, Zenaide M. N.^1,3 

[1] George Washington Univ, Sheikh Zayed Inst Pediat Surg Innovat, Childrens Natl Hlth Syst Sch Med & Hlth Sci, Childrens Res Inst,Div Anesthesiol Pain & Periope, Washington, DC 20010 USA

[2] Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, 930 Scaife Hall, Pittsburgh, PA 15213 USA

[3] George Washington Univ, Sch Med & Hlth Sci, Childrens Natl Hlth Syst, Ctr Neurosci Res,Childrens Res Inst, Washington, DC 20010 USA

关键词: Nicotine;    Nicotinic;    Autism;    Social behavior;    nAChR;    BTBR;    Nociception;    Nocifensive;    Pain;   

DOI  :  10.1016/j.neuropharm.2016.09.013

来源: Elsevier

【 摘 要 】

Caretakers and clinicians alike have long recognized that individuals with autism spectrum disorder (ASD) can have altered sensory processing, which can contribute to its core symptoms. However, the pathobiology of sensory alterations in ASD is poorly understood. Here we examined nocifensive behavior in ASD mouse models, the BTBR T(+)Itpr3(tf)/J (BTBR) and the fragile-X mental retardation-1 knockout (Fmr1-KO) mice. We also examined the effects of nicotine on nocifensive behavior given that nicotine, a nicotinic cholinergic receptor (nAChR) agonist that has antinociceptive effects, was shown to improve social deficits and decrease repetitive behaviors in BTBR mice. Compared to respective controls, both BTBR and Fmr1-KO had hyporesponsiveness to noxious thermal stimuli and electrical stimulation of C-sensory fibers, normal responsiveness to electrical stimulation of A beta- and A delta-fiber, and hyper responsiveness to visceral pain after acetic acid intraperitoneal injection. In BTBR, nicotine at lower doses increased, whereas at higher doses, it decreased hotplate latency compared to vehicle. In a significantly different effect pattern, in control mice, nicotine had antinociceptive effects to noxious heat only at the high dose. Interestingly, these nocifensive behavior alterations and differential responses to nicotine antinociceptive effects in BTBR mice were associated with significant downregulation of alpha 3, alpha 4, alpha 5, alpha 7, beta 2, beta 3, and beta 4 nAChR subunits in several cerebral regions both, during embryonic development and adulthood. Taken together, these findings further implicate nAChRs in behaviors alterations in the BTBR model and lend support to the hypothesis that nAChRs may be a target for treatment of behavior deficits and sensory dysfunction in ASD. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

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