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An inhalation method of ethanol administration was used to study the effects of 14 day, of ethanol administration on the immune and hematopoietic systems of the rat. A decrease in cellularity was found in the spleen, thymus, and bone marrow of ethanol-treated rats. Although the red blood cell count, white blood cell count, and hemoglobin concentration were not significantly different between treatment and control groups, treatment with ethanol altered the relative proportion of lymphocytes and polymorphonuclear leukocytes in the peripheral blood. The granulocyte-macrophage progenitor cells in the bone marrow were unaffected by ethanol treatment, but a significant decline in the number of erythroid progenitor cells warn noted in ethanol-treated rats. Splenic lymphocytes, although fewer in number in the ethanol-treated rats, showed no significant difference in ability to proliferate when stimulated by nonspecific mitogens [ABSTRACT FROM AUTHOR]

Previous study findings from this laboratory and other laboratories have established that ethanol administration to experimental animals or ingestion by human beings results in many changes in the immune system. The major effort in this laboratory is the study of the mechanisms by which ethanol down-regulates the responses of thymus-derived lymphocytes. By using a rat model of ethanol intoxication we have described a defect in lymphocyte proliferation to concanavalin A. In the current report data, preliminary and definitive, are presented that show our approach to determining the mechanisms of ethanol-associated impairments in the immune system, especially the defect in lymphocyte proliferation. We have found that purified thymus-derived lymphocytes from the spleens of ethanol-treated rats have an inherent defect in their response to mitogenic stimulation. This defect is not caused by the direct effects of ethanol on the cells and probably is not caused by an inability of the cells from ethanol-treated animals to produce the lymphocyte growth factor interleukin 2. Data are also presented that indicate that corticosteroids, produced most abundantly in this model by withdrawal from ethanol, play a role in the down-regulation of the response of spleen cells to mitogenic stimulation. [ABSTRACT FROM AUTHOR]

Background: A salient effect of addictive drugs is to hijack the dopamine reward system, an evolutionarily conserved driver of goal-directed behavior and learning. Reduced dopamine type 2 receptor availability in the striatum is an important pathophysiological mechanism for addiction that is both consequential and causal for other molecular, cellular, and neuronal network differences etiologic for this disorder. Here, we sought to identify gene expression changes attributable to innate low expression of the Drd2 gene in the striatum and specific to striatal indirect medium spiny neurons (iMSNs)., Methods: Cre-conditional, translating ribosome affinity purification (TRAP) was used to purify and analyze the translatome (ribosome-bound messenger RNA) of iMSNs from mice with low/heterozygous or wild-type Drd2 expression in iMSNs. Complementary electrophysiological recordings and gene expression analysis of postmortem brain tissue from human cocaine users were performed., Results: Innate low expression of Drd2 in iMSNs led to differential expression of genes involved in GABA (gamma-aminobutyric acid) and cAMP (cyclic adenosine monophosphate) signaling, neural growth, lipid metabolism, neural excitability, and inflammation. Creb1 was identified as a likely upstream regulator, among others. In human brain, expression of FXYD2 , a modulatory subunit of the Na/K pump, was negatively correlated with DRD2 messenger RNA expression. In iMSN-TRAP- Drd2 HET mice, increased Cartpt and reduced S100a10 (p11) expression recapitulated previous observations in cocaine paradigms. Electrophysiology experiments supported a higher GABA tone in iMSN- Drd2 HET mice., Conclusions: This study provides strong molecular evidence that, in addiction, inhibition by the indirect pathway is constitutively enhanced through neural growth and increased GABA signaling., (© 2022 The Authors.)