Prior nicotine self-administration attenuates subsequent dopaminergic deficits of methamphetamine in rats: role of nicotinic acetylcholine receptors

Abstract

Preclinical studies have demonstrated that oral nicotine exposure attenuates long-term dopaminergic damage induced by toxins, including repeated, high doses of methamphetamine. It is suggested that alterations in nicotinic acetylcholine receptor (nAChR) expression, including α4β2* and α6β2* subtypes, likely contribute to this protection. The current study extended these findings by investigating whether nicotine self-administration in male, Sprague-Dawley rats 1): attenuates short-term dopaminergic damage induced by methamphetamine and 2) causes alterations in levels of α4β2* and α6β2* nAChR subtypes. The findings indicate that nicotine self-administration (0.032 mg/kg/infusion for 14 days) per se did not alter α4β2* and α6β2* nAChR expression or dopamine transporter (DAT) expression and function. Interestingly, prior nicotine self-administration attenuated methamphetamine-induced decreases in DAT function when assessed 24 h, but not 1 h, after methamphetamine treatment (4 × 7.5 mg/kg/injection). The ability of nicotine to attenuate the effects of methamphetamine on DAT function corresponded with increases in α4β2*, but not α6β2*, nAChR binding density. Understanding the role of nAChRs in methamphetamine-induced damage has the potential to elucidate mechanisms underlying the etiology of disorders involving dopaminergic dysfunction, as well as to highlight potential new therapeutic strategies for prevention or reduction of dopaminergic neurodegeneration.

Sex-Specific Alterations of White Matter Developmental Trajectories in Infants With Prenatal Exposure to Methamphetamine and Tobacco

“…30 Together, these findings suggest that prenatal stimulant exposure might lead to epigenetic effects, with reduced myelin gene expression and less mature white matter development in the ACR of girls exposed to stimulants (especially tobacco). Unlike prior studies 68,69 that suggest nicotine's neuroprotective effects on methamphetamine-induced neurotoxic effects in adults, our methamphetamine/tobaccoexposed infants had greater white matter abnormalities.…”

Activation of α7nAChR Protects Against Gastric Inflammation and Dysmotility in Parkinson’s Disease Rats

“…It has been reported that nicotine can alleviate toxin-induced nigrostriatal damage by activating α7nAChR in the brain ( Baladi et al, 2016 ). To determine whether the PNU treatment-induced improvement in gastric motility in 6-OHDA rats was associated with the neuroprotective effect of α7nAChR activation in the brain, we examined tyrosine hydroxylase (TH) expression in the SN and ChAT expression in the dorsal medulla.…”