Dopamine D5 Receptor Expression is Unchanged in Peripheral Blood Lymphocytes in Essential Hypertension

The present study was designed to investigate possible changes in the expression of lymphocyte dopamine receptor in essential hypertension. The expression of dopamine D₅ receptor was evaluated by radioligand binding techniques using [³H]-SCH 23390 as ligand. Plasma catecholamines, aldosterone levels and plasma renin activity were also measured.

Eleven borderline hypertensive patients, 15 patients with mild essential hypertension, 7 patients with moderate essential hypertension and 5 patients with severe essential hypertension were examined. Plasma catecholamine levels were assayed by high pressure liquid chromatography with electrochemical detection. Dopamine D₅ receptor was measured by radioligand binding techniques. Plasma aldosterone levels and renin activity were determined by radio immunoassay.

[³H]-SCH 23390 was specifically bound to human peripheral blood lymphocytes. The binding was time-, temperature- and concentration- dependent with a dissociation constant (Kd) value of 0.59 nM and a maximum density of binding sites (Bmax) of 223 pmol/ 10⁶ cells.

Dopamine competed with [3H]-SCH 23390 binding in the submicromolar range suggestin the labelling of a dopamine D5 receptor. No changes in peripheral blood lymphocytes between essential hypertensive patients and normotensive subjects. Also catecholamines, plasma renin activity and aldosterone levels were unchanged.

In spite of the availability of a sensitive technique for measuring dopamine receptors in human peripheral lymphocytes, no change in their expression was noticeable in essential hypertension. This suggests that dopamine receptor analysis in essential hypertension is not a useful marker for investigating hypertension-dependent changes of the peripheral dopaminergic system. the density of [9 HI-SCH 23390 binding sites were observed in human     

Alterations of immune functions in heroin addicts

The alteration of peripheral blood T-and B-lymphocyte proliferative responses were determined during different periods of withdrawal in heroin (Hw) and heroin / bhang (HBw) addicts. The results clearly demonstrated a significant decrease in the response of T- lymphocytes to PHA-stimulation and secretion of IL-2 in both Hw and HBw addicts. The in vitro presence of naloxone induced further inhibition of the PHA proliferative response and IL-2 production. Our data also indicated a significant suppression of IFN-gamma levels by human blood lymphocytes from Hw and HBw addicts. Additionally, a significant suppression of IFN-gamma production was demonstrated in the presence of naloxone. Moreover, IL-4 production was suppressed in Hw, but not in HBw groups and the in vitro presence of naloxone did not affect the level of IL-4 in both groups. However, IL-10 production was significantly increased in both groups accompanied by a significant suppression of IL-10 secretion in the presence of naloxone. In contrast, IL-5 levels stimulated by PHA showed a significant increase in both groups, while no significant effect of naloxone could be observed. Our results suggested that heroin administration can cause measurable suppression of some components of the human cellular immune system. The results further demonstrated that the immunsuppressive effect observed after heroin use are naloxone-mediated and suggested that activation of the adrenal gland is one potential mechanism for this effect.     

c-fos and c-jun mRNA Expression in Activated Cord and Adult Lymphocytes: An Analysis by Northern Hybridization

Background and Objectives: To further analyze the neonatal immune response to an antigenic challenge such as blood transfusion, c-fos and c-jun mRNA expression were analyzed in twelve in-vitro-stimulated normal cord blood and ten in-vitro-stimulated normal adult peripheral blood lymphocyte samples. Materials and Methods: Lymphocyte samples were stimulated by either the mitogen phytohemagglutinin (PHA) or the monoclonal antibody αCD3. Proliferation rate and Northern blot hybridization were employed. Results: Cord lymphocytes revealed a greater proliferation rate with PHA and αCD3 than adult lymphocytes (p=0.0081 and 0.0023, respectively). In addition, Northern blot analysis of cord and adult samples revealed similar maximal increases in c-fos (99±15 and 126±11%, p=0.0126) and c-jun (123±9 and 185±38%, p=0.0291) mRNA expression, respectively, as early as 15 min postαCD3 stimulation. Adult lymphocytes showed an equivalent increase in mRNA expression of c-fos and c-jun (140±25 and 155±31%) at 30 min post-PHA stimulation, while cord lymphocyte maximum c-fos and c-jun expression (82±6 and 142±12%) occurred at 15 min post-PHA stimulation (c-fos, p=0.0354; c-jun, p=0.0112). Conclusion: Although cord lymphocyte proliferation rates were significantly greater than those of adult lymphocytes following stimulation, lymphocyte activation, as analyzed by c-fos and c-jun mRNA expression, appears similar in both cord and adult samples. We conclude that cord lymphocyte activation exhibits an adult-type profile.     

The apomorphine test in heroin addicts

Chronic administration of opiates to laboratory animals induces supersensitivity of the dopamine receptors in the cerebral areas innervated by the mesotelencephalic dopamine pathways. In humans, the in vivo study of the sensitivity of the dopamine neurotransmitter system in Parkinson's patients can be done by means of the apomorphine test, which consists of measuring the number of yawns induced by the subcutaneous administration of low doses of apomorphine (0.005 mg/kg). If chronic opiate use in humans, as in experimental animals, results in supersensitivity of the dopamine systems, the apomorphine test could differentiate between heroin addicts and healthy volunteers, with the former showing greater number of yawns. In order to test this hypothesis we carried out the apomorphine lest in two groups of subjects: a group of male heroin addicts attending our Addiction Treatment Centre for detoxification and the other group consisting of healthy volunteer male university students. Results showed that subcutaneous apomorphine administration induced a greater number of yawns (p < 0.05) in the group of heroin addicts as compared with the group of healthy volunteers, suggesting that heroin addicts present an enhanced sensitivity of the dopamine neurotransmitter system.     

THE DOPAMINERGIC SYSTEM IN HYPERTENSION

Dopamine exerts cardiovascular and renal actions mediated through interaction with specific dopamine receptors. Dopamine receptors are cell surface receptors coupled to G-proteins and classified into two main super families based on biochemical, pharmacological and molecular characteristics. The dopamine D1-like receptor super family includes D1 and D5 receptors, known also in rodents as D1A and D1B sites. These receptors are linked to stimulation of adenylate cyclase. The dopamine D2-like receptor super family includes D2, D3 and D4 receptors. These receptors are linked to inhibition of adenylate cylase or not related with this enzyme activity. They also interfere with opening of Ca⁺² channels and are linked to stimulation of K⁺ receptors. Dopamine receptor subtypes are expressed in brain as well as in extracerebral structures such as the heart, blood vessels, carotid body, kidney, adrenal gland, parathyroid gland and gastrointestinal tract.

In the kidney, which represents the peripheral organ where dopamine receptors were more extensively investigated, dopamine receptors are involved in regulation of hemodynamic, electrolyte and water transport, as well as renin secretion. Hypertension-related dopamine receptor changes were also investigated primarily in the kidney. Defective renal dopamine production and/or dopamine receptor function have been reported in human primary hypertension as well as in genetic models of animal hypertension. There may be a primary defect in D1-like receptors and an altered signalling system in the proximal tubules that lead to reduced dopamine-mediated effects on renal sodium excretion in hypertension. Studies on the influence of hypertension on dopamine D2-like receptors are sparse Disruption of either D1A or D3 receptors at the gene level causes hypertension in mice. Using peripheral blood lymphocytes as possible markers of the status of dopamine receptors in essential hypertension, no changes of dopamine D1-like receptors were noticeable, whereas an increase of dopamine D2-like receptors likely representing an up-regulation mechanism was reported. Available information collectively indicates an involvement of peripheral dopaminergic system in hypertension consisting either in impaired receptor transduction mechanisms and/or in receptor loss. A better knowledge of molecular bases of these changes may contribute to the development of specific therapeutic approaches in the future.     

THE EFFECT OF HEROIN ADDICTION ON PITUITARY-TESTICULAR FUNCTION

The effect of heroin addiction on pituitary-testicular function was studied in 54 active and 19 abstinent addicts and their results were compared with those of 43 age-matched controls. Abnormal sexual function was frequently found in heroin addicts and this persisted after drug withdrawal. The mean total (mean +/- SE, 18.1 +/- 1.0 nmol/1) and free (0.17 +/- 0.03 nmol/1) testosterone (T) levels in heroin addicts were significantly lower than those in healthy controls (total T 22.8 +/- 1.1 nmol/1), P less than 0.005; free T 0.30 +/- 0.03 nmol/1, P less than 0.005). The mean sex hormone binding globulin binding capacity was higher in heroin addicts (60.1 +/- 5.2 mM) than in healthy controls (35.5 +/- 2.1 mM). These hormonal changes returned promptly to normal after withdrawal. The basal LH and FSH and the responses to LHRH were comparable in the three groups studied. The finding of significantly lower total and free T together with higher SHBG indicates an abnormal testicular function in heroin addiction. Normal basal and LHRH-stimulated LH and FSH levels suggest that chronic heroin abuse depressed testicular function via the hypothalamus or higher centres.     

Cloning, molecular characterization, and chromosomal assignment of a gene encoding a second D1 dopamine receptor subtype: differential expression pattern in rat brain compared with the D1A receptor.

Multiple D1 dopaminergic receptor subtypes have been postulated on the basis of pharmacological, biochemical, and genetic studies. We describe the isolation and characterization of a rat gene encoding a dopamine receptor that is structurally and functionally similar to the D1 dopamine receptor. The coding region, which is intronless, encodes a protein of 475 amino acids (Mr 52,834) with structural features that are consistent with receptors coupled to guanine nucleotide-binding regulatory proteins. The expressed protein binds dopaminergic ligands and mediates stimulation of adenylyl cyclase with pharmacological properties similar to those of the D1 dopamine receptor. The gene encoding the human homologue of this receptor subtype is located to the short arm of chromosome 4 (4p16.3), the same region as the Huntington disease gene. In striking contrast to the previously cloned D1 receptor, little or no mRNA for the receptor described here was observed in striatum, nucleus accumbens, olfactory tubercle, and frontal cortex. High levels of mRNA for this receptor were found in distinct layers of the hippocampus, the mammillary nuclei, and the anterior pretectal nuclei, brain regions that have been shown to exhibit little or no D1 dopamine receptor binding. On the basis of its properties we propose that this dopamine receptor subtype be called D1B.     

Enhanced Expression of the Inhibitory Protein Gi2α and Decreased Activity of Adenylyl Cyclase in Lymphocytes of Abstinent Alcoholics

Ethanol exposure alters signal transduction through the adenylyl cyclase (AC) system. To elucidate the basis for this effect, we investigated the AC system in peripheral lymphocytes from abstinent alcoholic men ( n = 22), actively drinking alcoholic men ( n = 41), and nonalcoholic control men ( n = 16). Immunoblot analysis of lymphocyte membranes from abstinent alcoholics demonstrated a 3.0-fold increase in the level of G_i2α protein ( p < 0.05) compared with controls. However, levels of G_i2α protein were similar in both groups. Abstinent alcoholics had a 2.9-fold increase in G_i2α mRNA ( p < 0.001) and a 2.7-fold increase in G₂α mRNA ( p < 0.03) compared with lymphocytes from control subjects. Actively drinking alcoholics, in contrast, had unaltered G₂α protein, G_i2α protein, and G_i2α mRNA levels compared with control subjects, but did have a 1.8-fold increase ( p < 0.01) in G_i2α mRNA. Consistent with enhanced G_i2α expression, lymphocyte membranes from abstinent alcoholics had decreased basal, prostaglandin E_1-, guanosine 5'-0-(3-thiotriphosphate)-γS-, and forskolin-stimulated AC activity compared with both controls and actively drinking alcoholics ( p < 0.05). We conclude that lymphocyte AC is reduced during abstinence from alcohol and enhanced expression of the inhibitory G-protein, G_i2α, may account for this change.     

Plasma apo/lipoproteins disturbances as a precondition for metabolic syndrome in HCV seronegative heroin addicts

Background: Dyslipidemia in heroin addicts is considered to be a precondition for developing metabolic syndrome. Objectives: The aim was to evaluate the frequency in serum lipid disturbances of hepatitis C virus (HCV) seronegative heroin addicts; the capacity of high-density lipoprotein (HDL)-C and apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) for predicting hypertriglyceridemia/low HDL-C profile; correlation of HDL-C with the apoB/apoA-I and their correlation to plasma apo/lipoproteins. Materials and methods: Sixty-six heroin addicts, seronegative for HCV and HIV, without liver morphological changes were divided into two groups according to their decreased/normal HDL-C concentrations. Results: We registered decreased HDL-C in 58.8% of the addicts; decreased apoA-I in 50.9%, increased triglyceride (TGL) in 35.9%, and increased apoB/apoA-I in 3.8% of the patients; and 25.7% had hypertriglyceridemia/low HDL profile. Addicts with low HDL-C had higher TGL (1.73 ± .91 vs. 1.31 ± .71, pр = .02) compared with addicts with normal HDL-C and the controls. Low HDL-C group had higher apoB/apoA-I compared with addicts with normal HDL-C (.62 ± .28 vs. .42 ± .11, pр = .000). HDL-C inversely correlated to apoB/apoA-I (p = ?.452, pр = .001). ApoB/apoA-I showed stronger correlation with the observed apo/lipoproteins than the HDL-C. The logistic regression model showed that apoB/apoA-I index (OR 89.1, 95% CI 1.3–5971.2) is more significant predictor in developing hypertriglyceridemia/low HDL profile than HDL-C. Conclusion: Heroin addiction is associated with decreased plasma concentrations of HDL-C, apoA-I, apoB, and increased TGL concentrations. In heroin addicts, HDL-C concentrations are significantly associated with the apoB/apoA-I index, which correlates to all lipid fractions and is a stronger predictor of metabolic syndrome lipid profile in heroin addicts.     

Impact of in-patient research participation on subsequent heroin use patterns: implications for ethics and public health

Aims Research on drug dependence often involves the administration of drugs of abuse to experienced drug users under controlled laboratory conditions. The primary objective of this study was to assess whether participation in such research alters the frequency of heroin use by non‐treatment‐seeking opioid‐dependent volunteers after study completion. Design Data were examined from four in‐patient studies involving controlled opioid administration. Setting Substance Use Research Center at Columbia University, New York State Psychiatric Institute. Participants Sixty‐nine heroin‐dependent volunteers. Measurements Participants' self‐reported heroin use prior to and 1 month after study participation was compared using a Wilcoxon test. Because a number of participants reported that they had stopped using heroin, a logistic regression was used to identify correlates of heroin cessation 1 month after study completion. Findings One hundred and one participants entered laboratory studies and 69 completed them. Self‐reported heroin use significantly decreased 1 month after study participation [1.7 (±2.0) bags per day] compared to baseline [6.8 (±4.2) bags per day], P < 0.001 among the 69 completers. In addition, 42% of the completers were heroin‐abstinent 1 month after study completion. Being African American, having a history of opioid dependence treatment, reporting heavier heroin use at baseline and a longer history of heroin use were correlated with cessation of heroin use. Conclusions Participation in opioid administration studies does not increase subsequent heroin use and for some individuals leads to accessing opioid dependence treatment and cessation of heroin use in the short term.     

The dopaminergic system in hypertension

Dopamine exerts cardiovascular and renal actions mediated through interaction with specific dopamine receptors. Dopamine receptors are cell surface receptors coupled to G-proteins and classified into two main super families based on biochemical, pharmacological and molecular characteristics. The dopamine D1-like receptor super family includes D1 and D5 receptors, known also in rodents as D1A and D1B sites. These receptors are linked to stimulation of adenylate cyclase. The dopamine D2-like receptor super family includes D2, D3 and D4 receptors. These receptors are linked to inhibition of adenylate cylase or not related with this enzyme activity. They also interfere with opening of Ca+2 channels and are linked to stimulation of K+ receptors. Dopamine receptor subtypes are expressed in brain as well as in extracerebral structures such as the heart, blood vessels, carotid body, kidney, adrenal gland, parathyroid gland and gastrointestinal tract. In the kidney, which represents the peripheral organ where dopamine receptors were more extensively investigated, dopamine receptors are involved in regulation of hemodynamic, electrolyte and water transport, as well as renin secretion. Hypertension-related dopamine receptor changes were also investigated primarily in the kidney. Defective renal dopamine production and/or dopamine receptor function have been reported in human primary hypertension as well as in genetic models of animal hypertension. There may be a primary defect in D1-like receptors and an altered signalling system in the proximal tubules that lead to reduced dopamine-mediated effects on renal sodium excretion in hypertension. Studies on the influence of hypertension on dopamine D2-like receptors are sparse Disruption of either D1A or D3 receptors at the gene level causes hypertension in mice. Using peripheral blood lymphocytes as possible markers of the status of dopamine receptors in essential hypertension, no changes of dopamine D1-like receptors were noticeable, whereas an increase of dopamine D2-like receptors likely representing an up-regulation mechanism was reported. Available information collectively indicates an involvement of peripheral dopaminergic system in hypertension consisting either in impaired receptor transduction mechanisms and/or in receptor loss. A better knowledge of molecular bases of these changes may contribute to the development of specific therapeutic approaches in the future.     

Protective effects of mineralocorticoid receptor blockade against neuropathy in experimental diabetic rats

Aims: Mineralocorticoid receptor (MR) blockade is an effective treatment for hypertension and diabetic nephropathy. There are no data on the effects of MR blockade on diabetic peripheral neuropathy (DPN). The aim of this study was to determine whether MRs are present in the peripheral nerves and to investigate the effectiveness of MR blockade on DPN in streptozotocin (STZ)‐induced diabetic rats. Methods: Expression of MR protein and messenger RNA (mRNA) was examined in the peripheral nerves using Western blot analysis and RT‐PCR. We next studied the effects of the selective MR antagonist eplerenone and the angiotensin II receptor blocker candesartan on motor and sensory nerve conduction velocity (NCV), morphometric changes and cyclooxygenase‐2 (COX‐2) gene and NF‐κB protein expression in the peripheral nerves of STZ‐induced diabetic rats. Results: Expression of MR protein and mRNA in peripheral nerves was equal to that in the kidney. Motor NCV was significantly improved by 8 weeks of treatment with either eplerenone (39.1 ± 1.2 m/s) or candesartan (46.4 ± 6.8 m/s) compared with control diabetic rats (33.7 ± 2.0 m/s) (p < 0.05). Sensory NCV was also improved by treatment with candesartan or eplerenone in diabetic rats. Eplerenone and candesartan caused significant improvement in mean myelin fibre area and mean myelin area compared with control diabetic rats (p < 0.05). COX‐2 mRNA and NF‐κB protein were significantly elevated in the peripheral nerves of diabetic rats compared with control rats, and treatment with eplerenone or candesartan reduced these changes in gene expression (p < 0.05). Conclusion: MR blockade may have neuroprotective effects on DPN.     

Dexamethasone administration inhibits skeletal muscle expression of the androgen receptor and IGF‐1 – implications for steroid‐induced myopathy

Context Glucocorticoids are a well‐recognized cause of muscle weakness. The early effects of glucocorticoids on skeletal muscle (SkM) androgen and IGF‐1 pathways have not been previously investigated in human subjects. Objective To determine if administration of the potent glucocorticoid dexamethasone down‐regulates SkM androgen receptor and the IGF‐1 signalling pathway. Methods and subjects Twenty‐four subjects (12 men and 12 women), including 12 with type 2 diabetes and 12 nondiabetics were enrolled. Venous blood sampling and biopsy of vastus lateralis were performed before and after administration of oral dexamethasone 4 mg/day for 4 days. Main outcome measures Changes in plasma testosterone and IGF‐1, SkM androgen receptor mRNA, SkM IGF‐1mRNA and SkM IGF‐1 receptor mRNA by quantitative RT‐PCR after dexamethasone. Results Relative expression of SkM androgen receptor was similar in male (1·63 ± 0·37) vs. female (1·57 ± 0·30) subjects, despite the significant difference in plasma testosterone levels. Plasma IGF‐1 and SkM expression of IGF‐1 and IGF‐1 receptor were also similar between males and females. Following dexamethasone, there was a significant down‐regulation of SkM androgen receptor (1·60 ± 0·23 vs. 1·11 ± 0·16, P < 0·05) and IGF‐1 (1·72 ± 0·29 vs. 1·06 ± 0·14, P < 0·05) mRNA, but no change in expression of the IGF‐1 receptor. Plasma testosterone fell significantly in both sexes (male: 15·0 ± 1·3 vs. 11·3 ± 1·2 nmol/l, P < 0·01, female: 1·8 ± 0·5 vs. 0·5 ± 0·1 nmol/l, P < 0·05). Conclusions Exogenous steroid excess results in relative androgen deficiency at two levels, reduced circulating testosterone and SkM androgen receptor mRNA, along with reduced SkM IGF‐1 mRNA. These defects may contribute to the development of steroid‐induced myopathy.     

A twenty-year follow-up of narcotic addicts in Tucson, Arizona

This preliminary report from an epidemiological study of heroin addiction in Tucson, Arizona, 1956-1976, examines the status of heroin addicts 20 years after they have been identified as narcotics abusers, focusing on the maturation hypothesis which holds that heroin addicts tend to cease use of narcotics spontaneously by age forty. A cohort of 51 subjects was identified from Public Records of Court Appearances for narcotic offenses during a 36-month period (1955-1957), located and, where possible, interviewed. Records from a minimum of two agencies (law enforcement, corrections, treatment, welfare) were used to establish current status of the individual with reference to the use of narcotics and/or other drugs. Demographic, ethnic, socioeconomic makeup of the sample, as well as criminal involvement and treatment episodes, is included. After 20 years, one individual is drug-free or abstinent. Twenty-three are considered still addicted to heroin, 16 of these are in prison; seven are addicted to methadone or alcohol. Thirteen are dead. Six could not be located; however, five could be traced well beyond 1956 through criminal activities. All but one person have passed their fortieth birthdays. For these 51 addicts, the maturation hypothesis does not hold.     

Sodium salicylate restores the impaired insulin response to glucose and improves glucose tolerance in heroin addicts

Summary Plasma glucose, insulin, C-peptide, glucagon and growth hormone responses to intravenous glucose were evaluated in 10 heroin addicts in the basal state and during an infusion of sodium salicylate, an inhibitor of endogenous prostaglandin synthesis. Ten normal subjects, matched for age, sex and weight served as controls. In the basal state, the heroin addicts had markedly reduced insulin responses to intravenous glucose and low glucose disappearance rates (p<0.01vs controls). The infusion of sodium salicylate caused a striking increase of the acute insulin response to intravenous glucose (from 14.5±4 μU/ml to 88±11 μU/ml, p<0.001) and restored to normal the reduced glucose tolerance (K_G from 1.10±0.1% min⁻¹ to 2.04±0.19% min⁻¹). Hypoglycemic values were found in all addicts at the end of the test during salicylate infusion. Indomethacin pretreatment in five additional addicts also caused normalization of the impaired insulin responses to the intravenous glucose challenge and restored to normal the reduced glucose disappearance rate. Plasma glucagon and growth hormone levels were normally suppressed by glucose in addicts in basal conditions; sodium salicylate infusion completely overturned these hormonal responses which became positive in the first 15 min following the glucose challenge. These results demonstrate that the two prostaglandin synthesis inhibitors can restore the impaired B-cell response to glucose in heroin addicts to normal, indicating that this response is not lost but is inhibited by heroin itself or by other substances, perhaps by the endogenous prostaglandins.     

Abstinence From Moderate Alcohol Self-Administration Alters Progenitor Cell Proliferation and Differentiation in Multiple Brain Regions of Male and Female P Rats

Background: Acute and chronic ethanol exposure has been found to decrease hippocampal neurogenesis, reduce dendritic differentiation of new neurons, and increase cell death. Interestingly, abstinence from such treatment increases hippocampal neurogenesis and microglial genesis across several brain regions. The goal of the current investigation was to study cellular alterations on neuro‐ and cell‐genesis during abstinence following alcohol self‐administration using alcohol‐preferring rats (P rats). Methods: Male and female P rats were given the choice of drinking 10% alcohol in water or pure water for 7 weeks. Social interaction behavioral assessments were conducted at 5 hours upon removal of alcohol, followed by bromo‐deoxyuridine (BrdU, 150 mg/kg × 1/d × 14 d) injections to label proliferating cells. Animals were then killed 4 weeks later to conduct immunohistochemical and confocal analyses using antibodies against BrdU and other phenotypic markers (NeuN for mature neurons; Iba‐1 for microglia; GFAP for astrocytes; and NG₂ for oligodendrocyte progenitors). Results: Mild alcohol withdrawal anxiety was detected by reduction in social interactions. The number of hippocampal BrdU⁺ cells was increased approximately 50% during alcohol abstinence (26 ± 2.8 in controls vs. 39 ± 4 in alcohol group). BrdU⁺ cells were also increased in the substantia nigra (SN) approximately 65% in the alcohol abstinent group (12 ± 1 in controls vs. 19 ± 1.5 in alcohol group). No gender differences were found. Confocal analyses indicated that approximately 75% of co‐localization of BrdU⁺ cells with NeuN in the hippocampal dentate gyrus (DG) resulting a net increase in neurogenesis in the alcohol abstinent group compared to controls. In cingulum, greater proportion of BrdU⁺ cells were co‐localized with NG₂ in the alcohol abstinent group indicating increased differentiation toward oligodendrocyte progenitors in both genders. However, the phenotype of the BrdU⁺ cells in SN and other brain regions were not identified by NeuN, Iba‐1, GFAP, or NG₂ suggesting that these BrdU⁺ cells probably remain in a nondifferentiated stage. Conclusions: These data indicate that abstinence from moderate alcohol drinking increases hippocampal neurogenesis, cingulate NG₂ differentiation, and SN undifferentiated cell proliferation in both males and females. Such cellular alteration during abstinence could contribute to the spontaneous partial restoration of cognitive deficits upon sobriety.