Effects of Chronic Alcoholic Disease on Magnocellular and Parvocellular Hypothalamic Neurons in Men

Abstract

Although numerous data showing severe morphological impairment of magnocellular and parvocellular hypothalamic neurons due to chronic alcoholic consumption have been gathered from animal experiments, only one study (Harding et al., 1996) was performed on POST MORTEM human brain. This study showed a reduction in the number of vasopressin (VP)-immunoreactive neurons in the supraoptic (SON) and paraventricular (PVN) nuclei, but did not provide any data regarding the effect of chronic alcohol intake on human parvocellular neurons. In order to assess whether the changes observed in the animal model also occur in humans and provide a structural basis for the results of clinical tests, we performed immunohistochemical and morphometric analysis of magnocellular (VP and oxytocin, OT) and parvocellular (corticotropin-releasing hormone, CRH) neurons in post-mortem brains of patients afflicted with chronic alcoholic disease. We analyzed 26-male alcoholics and 22 age-matched controls divided into two age groups--"young" (< 40 yr) and "old" (> 40 yr). Hypothalamic sections were stained for OT, VP, and CRH. The analysis revealed: 1) decrease in VP-immunoreactivity in the SON and PVN as well as OT-immunoreactivity in the SON in alcoholic patients; 2) increase in OT-immunoreactivity in the PVN; 3) increase in CRH-immunoreactivity in parvocellular neurons in the PVN. Furthermore, the proportion of cells containing CRH and VP was increased in alcoholics. These findings indicate that chronic alcohol consumption does indeed impair the morphology of magnocellular neurons. The enhancement of CRH-immunoreactivity and increased co-production of CRH and VP in parvocellular neurons may be due to a decline in glucocorticoid production, implied by the hypoplasic impairment of adrenal cortex we observed in alcoholics during the course of this study.

Nucleus accumbens lentiviral-mediated gain of function of the oxytocin receptor regulates anxiety- and ethanol-related behaviors in adult mice

“…In support of this hypothesis, Silva and colleagues reported that prolonged alcohol intake leads to irreversible loss of oxytocin neurons in the PVN in Wistar rats [66]. In alcoholic humans, post-mortem brains of patients afflicted with chronic alcoholic disease showed increased oxytocin immunoreactivity in the PVN [7]. Very recently, Peters and co-workers have shown that acute intracerebroventricular (ICV) infusion of oxytocin (1 μg/5 μL) attenuated voluntary ethanol self-administration [67].…”

“…Oxytocin neurotransmission is thought to contribute to the activating and reinforcing effects of ethanol and other drugs of abuse [for review, see [3,4]]. Altered oxytocin neurotransmission has been observed in human alcoholics [5][6][7] and in several animal models of alcohol dependence [2,8,9]. It is believed that the oxytocin receptor (OxtR) mediates the involvement of the oxytocin system in psychiatric disorders in general and addiction in particular.…”

Residual social, memory and oxytocin-related changes in rats following repeated exposure to γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination

“…With respect to other classes of drugs of abuse, chronic morphine decreases brain OT synthesis (You et al 2000), chronic ethanol exposure causes degeneration of hypothalamic OT-containing magnocellular neurons (Sivukhina et al 2006) while repeated cocaine administration depletes hippocampal and hypothalamic OT (Sarnyai et al 1992). It is similarly possible that MDMA and GHB might deplete hypothalamic OT to cause alterations in OT-related gene expression.…”

Targeting the Oxytocin System to Treat Addictive Disorders: Rationale and Progress to Date

“…In alcoholic individuals, plasma OT levels were decreased (39) and OT immunoreactivity was decreased in the magnocellular neurons of the hypothalamus in a post-mortem study (40). Chronic exposure to Δ 9 – tetrahydrocannabinol in rats downregulated OT mRNA expression in the NAc and VTA (41).…”