Nicotine increases microdialysate brain amino acid concentrations and induces conditioned place preference

The action of nicotine on the nicotinic receptor-mediated release of inhibitory and excitatory acids in the nucleus accumbens, NAC, of freely moving rats was studied in order to clarify their effects' on reinforcing behavior as estimated by conditioned place preference (CPP). Using the technique of microdialysis, intraperitoneal (i.p.) injections of nicotine (0.15-0.3-0.6 mg/kg), significantly increased aspartate, glutamate, arginine, taurine, and alanine microdialysate content in the nucleus accumbens. The same doses of nicotine were able to elicit a reinforcing effect in a CPP paradigm which was probably associated with the increased brain levels of excitatory acids triggering additional dopamine release in the mesolimbic system. (c) 2005 Elsevier B.V and ECNP. All rights reserved

Ethanol but not acetaldehyde induced changes in brain taurine: a microdialysis study

Research has suggested that catalase plays a role in mediating ethanol's psychopharmacological effects. Catalase is an enzyme that oxidizes ethanol to acetaldehyde. It has been reported that when catalase activity is reduced by 3-amino-1,2,4-triazole (AT), rats reduce their intake and preference for ethanol. The present study assessed the effects of AT on the brain amino acids levels following ethanol administration in Wistar rats. The study consisted of three parts. In the first part, we found no effects of acute and chronic intraperitoneally administered acetaldehyde on amino acids dialysate levels in nucleus accumbens. In the second part, AT was administered five hours prior to ethanol or its vehicle. Ethanol significantly affected the levels of taurine in rat pre-treated with AT. In the final part, ethanol was administered following the pre-treatment with AT but the dependent variable was the concentration of ethanol in the brain

Endogenous sodium pump inhibitors and ageassociated increases in salt sensitivity of blood pressure in normotensives

AY, Lakatta EG. Endogenous sodium pump inhibitors and age-associated increases in salt sensitivity of blood pressure in normotensives. Am J Physiol Regul Integr Comp Physiol 294: R1248-R1254, 2008. First published February 20, 2008 doi:10.1152/ajpregu.00782.2007.-Factors that mediate increases in salt sensitivity of blood pressure with age remain to be clarified. The present study investigated 1) the effects of high-NaCl intake on two Na pump inhibitors, endogenous ouabain (EO) and marinobufagenin (MBG), in middle-aged and older normotensive Caucasian women; and 2) whether individual differences in EO and MBG are linked to variations in sodium excretion or salt sensitivity. A change from 6 days of a lower (0.7 mmol ⅐ kg Ϫ1 ⅐ day Ϫ1 )-to 6 days of a higher (4 mmol ⅐ kg Ϫ1 ⅐ day Ϫ1 )-NaCl diet elicited a sustained increase in MBG excretion that directly correlated with an increase in the fractional Na excretion and was inversely related to age and to an age-dependent increase in salt sensitivity. In contrast, EO excretion increased only transiently in response to NaCl loading and did not vary with age or correlate with fractional Na excretion or salt sensitivity. A positive correlation of both plasma and urine levels of EO and MBG during salt loading may indicate a casual link between two Na pump inhibitors in response to NaCl loading, as observed in animal models. A linear mixed-effects model demonstrated that age, dietary NaCl, renal MBG excretion, and body mass index were each independently associated with systolic blood pressure. Thus, a sustained increase in MBG in response to acutely elevated dietary NaCl is inversely linked to salt sensitivity in normotensive middle-aged and older women, and a relative failure of MBG elaboration by these older persons may be involved in the increased salt sensitivity with advancing age. marinobufagenin; ouabain; hypertension NUMEROUS STUDIES HAVE REPORTED that the magnitude of the systolic blood pressure (SBP) response to acute changes in dietary NaCl intake, i.e., salt sensitivity of blood pressure, increases with advancing age NaCl ingestion results in an increase in plasma volume and natriuresis. It has been postulated for some time that endogenous substances [sodium pump inhibitors (SPI)] are stimulated by increased Na intake and increase natriuresis by inhibiting renal tubular Na pumps to prevent renal reabsorption of filtered Na More recently, SPI assays have improved and become more specific That age-associated differences in circulating endogenous Na pump inhibitors may be implicated in the age-associated increase in SBP and increased NaCl sensitivity of SBP in older humans has been suggested previously (21) but never tested. The goal of the present study was to investigate effects of a subacute change in dietary NaCl on urinary and plasma EO and MBG in middle-aged and older normotensive subjects, and to determine whether NaCl-induced individual differences in the levels of these substances are linked to variations in renal sodium excretion or salt sensitivity of SBP. METHODS Subjects: inclusion and exclusion criteria. MBG and EO were measured in a series of healthy Caucasian women, ages 40 -70 yr, who, as part of another study, were salt restricted and then salt loaded to determine interactions among breathing patterns, PCO 2, and arterial pressure (2). Determination of subject eligibility involved telephone interview, physical examination, and informed consent. Inclusion and exclusion criteria also include the following: all qualified candidates were normotensive (resting SBP, Ͻ139 mmHg and resting diastolic blood pressure, Ͻ89 mmHg); had no history of respiratory, cardiovascular, liver or kidney disease, or diabetes; were free of cardiac organ damage determined by electrocardiogram; and were free of kidney dysfunction as determined by plasma creatinine Ͼ1.5. Subjects treated with estrogens or nonsteroidal anti-inflammatory agents, or medications affecting sodium, potassium, calcium, water, hemodynamic, or neural regulation (including diuretics, steroids, major tranquilizers, narcotics, or benzodiazepines) were also excluded, as were smokers or those with body mass index (BMI) of Ͻ19 or Ͼ30. The protocol of the study was approved by the Medstar Research Institute Institutional Review Board, and all study subjects signed informed consents. Experimental design. The experiment consisted of a 12-day, outpatient, dietary intervention, including 6 days on a low-sodium (0.7 mmol⅐kg Ϫ1 ⅐day Ϫ1 ), low-potassium (0.7 mmol⅐kg Ϫ1 ⅐day Ϫ1 ) diet, followed immediately by 6 days on a high-sodium (4 mmol⅐kg Ϫ1 ⅐day Ϫ1 ), low-potassium (0.7 mmol⅐kg Ϫ1 ⅐day Ϫ1 ) diet. The average recommended dietary sodium intake in the American diet for an average-sized adult i