Abstract
Acetaldehyde (ACD), the first alcohol metabolite, plays a pivotal role in the rewarding, motivational, and addictive properties of the parental compound. Many studies have investigated the role of ACD in mediating neurochemical and behavioral effects induced by alcohol administration, but very little is known about the modulation of neuropeptide systems following ACD intoxication and withdrawal. Indeed, the neuropeptide Y (NPY) system is altered during alcohol withdrawal in key regions for cerebrocortical excitability and neuroplasticity. The primary goal of this research was to investigate the effects of ACD intoxication and withdrawal by recording rat behavior and by measuring NPY immunoreactivity in hippocampus and NAcc, two brain regions mainly involved in processes which encompass neuroplasticity in alcohol dependence. Furthermore, on the basis of the involvement of endocannabinoidergic system in alcohol and ACD reinforcing effects, the role of the selective CB1 receptor antagonist AM281 in modulating NPY expression during withdrawal was assessed. Our results indicate that (i) ACD intoxication induced a reduction in NPY expression in hippocampus and NAcc; (ii) symptoms of physical dependence, similar to alcohol’s, were scored at 12 h from the last administration of ACD; and (iii) NPY levels increased in early and prolonged acute withdrawal in both brain regions examined. The administration of AM281 was able to blunt signs of ACD-induced physical dependence, to modulate NPY levels, and to further increase NPY expression during ACD withdrawal both in hippocampus and NAcc. In conclusion, the present study shows that complex plastic changes take place in NPY system during ACD intoxication and subsequent withdrawal in rat hippocampal formation and NAcc. The pharmacological inhibition of CB1 signaling could counteract the neurochemical imbalance associated with ACD, and alcohol withdrawal, likely boosting the setting up of homeostatic functional recovery.
Highlights
Acetaldehyde (ACD), the first oxidation product of alcohol, is one of the mediators of the peripheral and central effects of alcohol [1,2,3,4,5], in particular playing a main role in the rewarding, motivational, and addictive properties of the parental compound [6,7,8]
Lower levels of neuropeptide Y (NPY)-IR in hippocampus, amygdala, and frontal cortex have been reported in selectively bred alcoholpreferring rats compared to non-preferring rats [24], as well as lower expression in NPY protein in NAcc has been measured in C57BL/6J mice, that innately consume larger amount of alcohol [25]
In the current study, the primary goal was to verify if ACD, the first metabolite of alcohol, is able to produce alterations in NPY protein levels in hippocampus and ventral striatum neurons, as already shown for alcohol [51, 64,65,66]
Summary
Acetaldehyde (ACD), the first oxidation product of alcohol, is one of the mediators of the peripheral and central effects of alcohol [1,2,3,4,5], in particular playing a main role in the rewarding, motivational, and addictive properties of the parental compound [6,7,8]. ACD is able to induce and maintain an operant drinking behavior and relapse following repeated forced abstinence [6] and to increase the firing rate, spikes/burst, and burst firing of VTA neurons [9,10,11]; the pharmacological manipulation of dopaminergic D2 and endocannabinoidergic CB1 receptors decreases its motivational and incentive value [8, 12]. NPY, a 36-amino acid peptide neuromodulator largely distributed in the central nervous system, is implicated in a wide range of functions including feeding, anxiety, seizures, circadian rhythms, memory, and cardiovascular regulation [18,19,20,21], besides its involvement in the neuronal mechanisms of alcohol consumption [22, 23]. Intracerebroventricular infusion of NPY produces electrophysiological effects similar to those of alcohol in rats [26]; consistently, NPY-deficient mice drink more alcohol www.frontiersin.org
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
