Motor Stimulant Effects of Ethanol Injected into the Substantia Nigra Pars Reticulata: Importance of Catalase-Mediated Metabolism and the Role of Acetaldehyde

Abstract

A series of experiments was conducted to investigate the locomotor effects of local injections of ethanol and the ethanol metabolite, acetaldehyde, into substantia nigra pars reticulata (SNr). Infusions of ethanol into SNr resulted in a dose-related increase in locomotor activity, with maximal effects at a dose of 1.4 mmol. Ethanol injected into a control site dorsal to substantia nigra failed to stimulate locomotion, and another inactive site was identified in brainstem areas posterior to substantia nigra. The locomotor effects of intranigral ethanol (1.4 mmol) were reduced by coadministration of 10 mg/kg sodium azide, a catalase inhibitor that acts to reduce the metabolism of ethanol into acetaldehyde in the brain. SNr infusions of acetaldehyde, which is the first metabolite of ethanol, also increased locomotion. Taken together, these results indicate that SNr is one of the sites at which ethanol and acetaldehyde may be acting to induce locomotor activity. These results are consistent with the hypothesis that acetaldehyde is a centrally active metabolite of ethanol, and provide further support for the idea that catalase activity is a critical step in the regulation of ethanol-induced motor activity. These studies have implications for understanding the brain mechanisms involved in mediating the ascending limb of the biphasic dose-response curve for the effect of ethanol on locomotor activity.

Locomotor stimulant effects of acute and repeated intrategmental injections of salsolinol in rats: role of μ-opioid receptors

“…The dose-response curve for Sal has an inverted U-shaped profile, with a peak at the 30.0-pmol dose. The profile of this plot is similar to those obtained in the posterior VTA for Sal (Rodd et al 2008), ethanol (Rodd et al 2004a, b), and ACH (Rodd et al 2004b;Rodd-Henricks et al 2002) in ICSA experiments and for ethanol in the substantia nigra pars reticulata (Arizzi-LaFrance et al 2006) in locomotor activity studies in rats. It is important to realize that the maximum effect on motor activity was obtained in our present study with the 30.0-pmol dose, which is clearly lower than that previously reported by our group for ethanol (150 nmol) and ACH (250 nmol; Sánchez-Catalán et al 2009).…”

Motor stimulant effects of ethanol and acetaldehyde injected into the posterior ventral tegmental area of rats: role of opioid receptors

“…Previously, Arizzi-LaFrance et al (2006) had reported that microinjections of ethanol or ACH into the SNr increased the locomotor activity of rats at doses higher than 350 nmol. The effective dose in our study was slightly lower than those reported in the aforementioned study: in our experiments, a 75-nmol dose of ethanol and a 250-nmol dose of ACH effectively and significantly increased the locomotor activity of rats.…”

“…The experiment was designed to assess the effects of intra-VTA injections of vehicle, ethanol (75 and 150 nmol), and ACH (25 and 250 nmol) on locomotor activity. Doses of ethanol and ACH were selected according to the dose-effect curves reported by Arizzi-LaFrance et al (2006) in their study on the locomotor-activating effects of the intranigral administration of these compounds. Based on the results of this experiment, the 150-nmol dose of ethanol and the 250-nmol dose of ACH were used in experiments 2 and 3b, respectively.…”

“…The work of Arizzi-laFrance et al (2006) is likely to be the first to investigate the neuroanatomy of this phenomenon. In their study, the authors identified the substantia nigra pars reticulata (SNr) as one of the anatomical sites at which ethanol may act to induce locomotor activation.…”

Reduction in Central H2O2Levels Prevents Voluntary Ethanol Intake in Mice: A Role for the Brain Catalase-H2O2System in Alcohol Binge Drinking

“…As noted earlier, the first product coming from brain-EtOH metabolism by the activity of Compound I is acetaldehyde. Acetaldehyde is a psychoactive molecule that, when administered centrally, exerts a broad range of behavioral (Arizzi-LaFrance et al, 2006;Rodd-Henricks et al, 2002;Smith et al, 1984) and neurochemical (Diana et al, 2008;Enrico et al, 2009;Foddai et al, 2004;Sirca et al, 2011) effects that are similar to those induced by EtOH in rodents. For this reason, it has been proposed that brain-EtOH-derived acetaldehyde could play a role in some of the psychopharmacological effects caused by EtOH.…”