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C E Johanson

Publications and source records attributed to C E Johanson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Benzodiazepine receptors mediate regional blood flow changes in the living human brain.

We studied the effects of a high-affinity gamma-aminobutyric acid (GABA)-benzodiazepine-receptor agonist (lorazepam) and an antagonist (flumazenil) in humans, using H2(15)O positron-emission tomography. Administration of lorazepam to healthy volunteers caused time- and dose-dependent reductions in regional cerebral blood flow and self-reported alterations in behavioral/mood parameters. Flumazenil administration reversed these changes. These observations indicated that benzodiazepine-induced effects on regional cerebral blood flow and mood/behavior are mediated at some level through GABA-benzodiazepine receptors, although the specific mechanism remains unclear. The approach described here provides a method for quantifying GABA-benzodiazepine-receptor-mediated neurotransmission in the living human brain and may be useful for studying the role of these receptors in a variety of neuropsychiatric disorders.

Adult↗
PubMed1995

Conditioned reinforcing effects of capsules associated with high versus low monetary payoff.

The ability of a placebo drug capsule to serve as a conditioned reinforcer as a function of being paired with money reinforcement was evaluated. Volunteers were administered two differently colored capsules that presumably contained two different drugs. Although the volunteers were told they might contain a stimulant, sedative, or placebo, both capsules contained only a placebo. During sessions, volunteers participated in performance tasks. The tasks were programmed so that following one capsule, the amount of money obtained contingent upon responding was greater (high frequency of reinforcement) than following the other capsule (low frequency of reinforcement). During experiment 1, participants were exposed twice each to the two reinforcement conditions (sampling). During these choice sessions, 9 of 12 participants chose the capsule associated with the high frequency of reinforcement 2 or 3 times. Experiment 2 was designed to explore further whether the differential mood effects observed during sampling sessions could be conditioned. Although this could not be demonstrated, the self-administration results demonstrating the control of choice behavior even in the absence of pharmacological effects suggest that drugs may function as conditioned reinforcers. This finding has implications for broadening our understanding of the determinants of initiation and continued drug use.

Adult↗
PubMed1995

The role of angiotensin II in the regulation of blood flow to choroid plexuses and cerebrospinal fluid formation in the rat.

The effect of peripherally administered angiotensin II (AII) on blood flow to choroid plexuses was examined in pentobarbital-anesthetized rats. The indicator fractionation method with 123I- or 125I-N-isopropyl-p-iodoamphetamine as the marker was employed to measure blood flow. Basal blood flow to choroid plexus of the lateral cerebral ventricle (LVCP) (3.19 +/- 0.23 ml g-1 min-1) was lower than that to choroid plexuses of the third (3VCP) and fourth (4VCP) ventricles (3.90 +/- 0.38 and 3.95 +/- 0.36 ml g-1 min-1, respectively). The effect of AII on choroidal blood flow varied depending on peptide dose and anatomical location of the choroidal tissue. AII infused intravenously at rates of 30 and 50 ng kg-1 min-1 decreased blood flow to both LVCP and 4VCP by 12-20%. Both lower (10 ng kg-1 min-1) and higher (100 and 300 ng kg-1 min-1) AII doses did not alter blood flow to LVCP and 4VCP. Blood flow to the 3VCP was not affected by any dose of the peptide used. In comparison, blood flow to cerebral cortex increased by 33% during intravenous AII infusion at a rate of 300 ng kg-1 min-1. The choroidal blood flow-lowering effect of moderate AII doses was abolished by both AT1 (losartan) and AT2 (PD 123319) receptor subtype antagonists (3 mg kg-1 i.v.). To determine whether the hemodynamic changes observed in choroid plexuses with moderate AII doses influence CSF formation, the ventriculocisternal perfusion was performed in rats (under the experimental conditions described) with Blue Dextran 2000 as the indicator.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

N-acetylcysteine enhances hippocampal neuronal survival after transient forebrain ischemia in rats.

BACKGROUND AND PURPOSE: Free radical scavengers enhance neuronal survival in some models of transient forebrain ischemia. Recent experiments have suggested that N-acetylcysteine prevents cellular injury after a reperfusion injury. No information is available regarding the neuroprotective potential of the free radical scavenger N-acetylcysteine after transient forebrain ischemia. In this study we evaluated the potential of N-acetylcysteine to improve hippocampal neuronal survival after transient forebrain ischemia in the rat. METHODS: In series A and B, ventilated, paralyzed, normothermic rats had 10 minutes of transient forebrain ischemia induced by bilateral carotid occlusion with hypotension induced by blood withdrawal (mean arterial blood pressure, 45 mm Hg). In series A, animals were administered N-acetylcysteine (163 mg/kg) 30 minutes and 5 minutes before transient forebrain ischemia. In series B, N-acetylcysteine (326 mg/kg) was administered 15 minutes after transient forebrain ischemia. In series C, N-acetylcysteine (326 mg/kg) was administered 15 minutes after transient forebrain ischemia in animals with a mean arterial blood pressure of 30 mm Hg during transient forebrain ischemia. All series had normal control, sham, and vehicle treatment groups. In all series, the rats were allowed to recover and were killed at 7 days after ischemia. The effect of forebrain ischemia was assessed by evaluating the number of viable neurons at bregma sections -3.3, -3.8, and -4.3 of the CA1 region of the hippocampus. RESULTS: The results demonstrated no physiological difference among the various treatment groups. There were no differences in the number of viable neurons between the transient forebrain ischemia with no treatment group and the vehicle (saline)-treated transient forebrain ischemic groups. Animals pretreated with N-acetylcysteine (mean number of neurons, 84 +/- 6) had a significant increase (P < .05) in neuronal survival compared with vehicle-treated animals (mean number of neurons, 43 +/- 4). Animals posttreated with N-acetylcysteine (mean number of neurons, 89 +/- 9) had a significant increase in neuronal survival compared with vehicle-treated animals (mean number of neurons, 7 +/- 1). However, N-acetylcysteine protection was only partial at 45 mm Hg and did not improve neuronal survival (mean number of neurons, 22 +/- 3) in animals with a more severe ischemic insult (mean arterial blood pressure, 30 mm Hg during transient forebrain ischemia) compared with vehicle-treated animals (mean number of neurons, 10 +/- 1). CONCLUSIONS: N-Acetylcysteine partially improved neuronal survival when administered before or after ischemia following transient cerebral ischemia (mean arterial blood pressure, 45 mm Hg) but not with a more severe ischemic insult of 10 minutes of transient cerebral ischemia with a mean arterial blood pressure of 30 mm Hg.

Acetylcysteine↗
PubMed1994

AT1 receptor subtype mediates the inhibitory effect of central angiotensin II on cerebrospinal fluid formation in the rat.

The effect of central administration of angiotensin II (AII) on cerebrospinal fluid (CSF) formation was studied in pentobarbital-anesthetized, artificially-ventilated rats. CSF production was measured by the ventriculocisternal perfusion method with Blue Dextran 2000 as the indicator. Baseline value of CSF production was 3.35 +/- 0.08 microliters/min. Intracerebroventricular (i.c.v.) infusion of AII at rates of 0.5 and 5 pg/min significantly lowered (P < 0.01) CSF formation by 23% and 16%, respectively. In comparison, high peptide doses (50 and 500 pg/min) did not alter this parameter. The inhibitory effect of low AII doses on CSF formation was blocked by the i.c.v. AT1 receptor subtype antagonists, losartan and SK&F 108566 (2.4 and 2.7 ng/min, respectively), but not by the AT2 receptor subtype-specific agent, PD 123319 (3.8 ng/min). Peptide AII antagonists, [Sar1,Ile8]AII (5 ng/min), which binds to both AT1 and AT2 receptors, had a similar effect to those of AT1-specific blockers. It is concluded that AII, by controlling CSF formation, may influence the water and electrolyte balance in the brain.

Angiotensin II↗
PubMed1994

Microdialysis analysis of effects of loop diuretics and acetazolamide on chloride transport from blood to CSF.

With the hypothesis that the NaCl cotransporter in mammalian choroid plexus (CP) has a role in CSF formation, we postulated that loop diuretic agents would curtail transport of Cl from blood to CSF. Microdialysis in the cisterna magna of Sprague-Dawley rats was used to assess the ability of furosemide and ethacrynic acid (i.e. loop agents that interfere directly with cotransport) to inhibit 36Cl transport from blood to CSF over a 3-h period. Cl uptake by CSF was quantified as % volume of distribution (Vd) of 36Cl, i.e. 100 x cpm/g CSF divided by cpm/ml plasma. Uptake curves of Vd vs. time were constructed for the various treatments; then, to compare drug effects, the curves were analyzed for: (i) the early slope of uptake (Kin), (ii) the steady-state value for Vd, and (iii) the area-under-curve (AUC). Assessment of the curve parameters collectively revealed that at 5 mg/kg, both furosemide (FUR) and ethacrynic acid (EA) reduced Cl penetration into CSF by one quarter; at 50 mg/kg, these loop agents decreased Cl uptake by about a third. On the other hand, 50 mg/kg of the carbonic anhydrase inhibitor, acetazolamide, reduced Cl uptake into CSF by 55-60%. Thus, NaCl cotransport inhibitors maximally reduced Cl transport in the rat by about 35%; this inhibition was less extensive than that brought about by acetazolamide, which interferes with CSF secretion by a different mechanism.

Acetazolamide↗
PubMed1994

Potassium efflux from infant and adult rat choroid plexuses: effects of CSF anion substitution, N-ethylmaleimide and Cl transport inhibitors.

To analyze interdependent transport of K and Cl, we investigated Rb (K) efflux from in vitro choroid plexus (CP) in isotonic artificial CSF (aCSF) medium containing anions or agents that alter KCl transport. Lateral ventricle CP was loaded with 86Rb for release to enable calculation of the efflux rate coefficient, k. With Cl as the main anion in control aCSF, the k value for 86Rb (K) in CP of 1 week infant rats (0.177 min-1) was 19% lower than in adults (0.218 min-1) (P < 0.005). Replacing CSF Cl with NO3 or SCN, respectively, reduced k for K in infant CP by 73% and 43%; similar anion selectivity was observed in adult tissues (P < 0.05). N-Ethylmaleimide (NEM), which stimulates KCI cotransport, significantly enhanced K efflux in infants and adults. In adult CP, the KCl cotransport inhibitor, furosemide (1 mM), decreased K efflux by 23% or 65%, respectively, when aCSF had Cl or NO3 as the main anion. In infant rat CP, 0.1 mM bumetanide (another KCl cotransport inhibitor), reduced k for K by 65%, whereas the Cl channel blocker diphenylamine carboxylate (1 mM) did not significantly alter K efflux. The collective findings for rat CP indicate a substantial component of K efflux that is associated with Cl concentration and the Cl transport protein sensitive to loop diuretics and NEM. The Cl-dependent K efflux is present in infants.

Aging↗
PubMed1994

A developmental analysis of differences in the uptake of [123I]isopropyliodoamphetamine versus 99mTc-pertechnetate by the choroid plexus and brain.

The uptake of intravascular [123I]isopropyliodoamphetamine (IMP) and 99mTc-pertechnetate into choroid plexus (CP) and brain (frontal cortex) was studied by an indicator fractionation method applied to immature, ketamine-anesthetized Sprague-Dawley rats (1.5, 2, and 3 wk). Assessment of the rate and extent of uptake of these indicators provides functional information (eg blood flow; transport) about various regions of the developing CNS. IMP uptake by lateral ventricle CP was 1.15 ml/g/min in 1.5-wk-old infant rats and gradually increased to 3.9 mg/g/min by adulthood (7-8 wk) (P < 0.05); over the same postnatal period, 99mTc uptake went from 2.82 to 3.18 ml/g/min. IMP uptake by cortex was 0.39 and 0.99 ml/g/min in infants and adults, respectively (P < 0.05); however, 99mTc uptake by cortex was only 0.07 +/- 0.01 ml/g/min at all ages, reflecting early development of blood-brain barrier (BBB) to pertechnetate. Overall, our findings indicated a progressive increase with age in the rate of uptake of IMP by CP and brain; and that 99mTc penetration into CP was relatively constant and substantially greater than into cortex at all developmental stages. Thus the nature of uptake of IMP, relative to 99mTc, was markedly different at the blood-cerebrospinal fluid barrier (i.e., CP) vs. the blood-brain barrier.

Aging↗
PubMed1994

Postnatal developmental changes in blood flow to choroid plexuses and cerebral cortex of the rat.

Postnatal developmental changes in blood flow to choroid plexuses of the lateral (LVCP) and fourth (4VCP) ventricles and cerebral cortex were studied in pentobarbital-anesthetized rats at 2, 3, 5, and 7-8 wk. Blood flow was measured by indicator fractionation with N-isopropyl-p-[125I]iodoamphetamine as the marker. Blood flow to the LVCP and 4VCP was 2.5 +/- 0.1 and 2.7 +/- 0.1 ml.g-1.min-1, respectively, and did not change between the 2nd and 3rd wk. However, it increased by 34% between the 3rd and 5th wk. From the age of 5 wk on, 4VCP was characterized by higher blood flow rates than LVCP. Cerebral cortical blood flow gradually increased between the 2nd and 5th wk. There was no difference in cortical blood flow between 5-wk-old and adult animals. The changes in choroidal blood flow likely represent a continuing adjustment of the choroidal vascular system to steadily increasing secretory capabilities of the maturing choroidal epithelium.

Aging↗
PubMed1993

Development of chloride transport by the rat choroid plexus, in vitro.

The uptake and efflux of 36Cl in the lateral ventricle choroid plexus of 1-7-week-old rats were measured to determine if Cl transport changed with age and if such transport responded to inhibitors of CSF secretion and ion transport. The steady-state (30 min) Cl uptakes were 148 +/- 9.4 nmol.mg-1 dry weight at 1 week and 139 +/- 7.0 nmol.mg-1 dry weight at 7 weeks, (P > 0.05). The 36Cl efflux was significantly slower in 1 and 2 week plexuses compared to more mature tissues (P < 0.01) with k (rate coefficient) = 0.029 +/- 0.004 s-1, t1/2 = 24.1 +/- 3.3 s at 1 week and k = 0.041 +/- 0.003 s-1, t1/2 = 17.4 +/- 1.3 s at 7 weeks. 36Cl efflux at 1 week was unaffected by acetazolamide, bumetanide and DIDS (4,4 diisothiocyanato-stilbene-2,2 disulphonic acid), however, all these drugs substantially reduced efflux from 2, 3 and 7 week choroid plexuses. In contrast, the Cl conductance blocker, DPC (diphenylamine carboxylate) at 10(-4) M reduced 36Cl efflux from both 1 and 7 week tissues by 43% and 39%, respectively. These findings suggest that some transport systems responsible for movement of Cl out of the epithelium are either absent or less functional in the immature rat choroid plexus and may account for the relatively low level of CSF secretion in younger animals. The unidirectional efflux of 36Cl, J, was calculated for 1 week and adult rats, as a function of the choroid plexus volume to surface area ratio (V/A).(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1993

Reproducibility of resting cerebral blood flow measurements with H2(15)O positron emission tomography in humans.

Two consecutive measurements of resting CBF were carried out in normal volunteers (n = 25) using H2(15)O positron emission tomography. Absolute whole-brain blood flow (WBBF; ml 100 g-1 min-1, mean +/- SD) for the first (40.3 +/- 6.4) and second (39.3 +/- 6.5) measurements was not significantly different (mean % difference 2.3 +/- 8.7). Analysis of regions of interest showed no significant differences in absolute regional CBF (rCBF) and normalized (rCBF/WBBF) rCBF. Left-right differences were also not significant. These data demonstrate the reproducibility of resting CBF measurements in normal humans.

Adult↗
PubMed1993

The discriminative stimulus effects of cocaine in pigeons.

Eight White Carneau pigeons were trained to discriminate 1.0 or 1.7 mg/kg of cocaine from saline. A fixed number of consecutive key peck responses on one key after the administration of cocaine resulted in 4-sec access to mixed grain. The same number of consecutive responses on the other key after saline also produced food. Different doses of cocaine and other drugs were tested to determine their ability to substitute (80% or more responding on the cocaine-appropriate key). The test drugs were selected to determine the selectivity of the cocaine discrimination in pigeons as well the role of different monoamines in mediating this behavioral effect. The drugs included other psychomotor stimulants, antidepressants, clonidine, yohimbine, other dopamine (1-(2-[bis(4-fluoro-phenyl)-methoxy]ethyl)4-3-phenylpropyl piperazine, GBR 12909) and serotonin (5-HT, sertraline) reuptake blockers, a D1 (SKF 75670), D2 (quinpirole), and 5-HT1A (8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT) agonist as well as the 5-HT3 antagonists, MDL 72222, LY 278584 and ondansetron. In addition, prazosin, an alpha 1 adrenergic antagonist, SCH 23390, a D1 antagonist; raclopride, a D2 antagonist and 1-(2-methoxyphenyl)-4-[4-(2-phthalimmido)butyl]piperazine (NAN-190), a putative 5-HT1A antagonist, were given in combination with cocaine to determine their ability to block the discriminative stimulus (DS) effects of cocaine, i.e., reduce drug-appropriate responding to 20% or less. The psychomotor stimulants, d-amphetamine and d-methamphetamine, completely substituted for cocaine and were similar in potency to each other and cocaine. The antidepressants I-deprenyl, imipramine, tomoxetine and bupropion also occasioned cocaine-appropriate responding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cyclic AMP alteration of chloride transport into the choroid plexus-cerebrospinal fluid system.

The permeation of 36Cl from blood into choroid plexus (CP) and cerebrospinal fluid (CSF) was studied in adult rats intraventricularly injected with either dibutyryl (db)-cAMP, theophylline with db-cAMP, or forskolin. All 3 treatments significantly enhanced the 15-min distribution (Vd) of 36Cl into CSF, by an average of 17-33%. In contrast, ouabain and acetazolamide (inhibitors of CSF production) reduced 36Cl uptake into CSF by 34% and 13%, respectively. A correlative analysis of the various treatments revealed that the volume of distribution of 36Cl in CSF varied inversely with that in the choroid plexus. This inverse relationship suggests drug effects on Cl movement across the apical (CSF-facing) membrane of CP.

Acetazolamide↗
PubMed1992

Ethacrynic acid and furosemide alter Cl, K, and Na distribution between blood, choroid plexus, CSF, and brain.

Can loop diuretics like ethacrynic acid and furosemide, when administered intravenously, significantly alter ion transport and fluid dynamics in CNS? To shed light on this unresolved issue, we tested the ability of these agents to effect redistribution of Na, K and Cl in adult rat brain. Cl penetration into various CNS regions was assessed as the volume of distribution, i.e., uptake, of 36Cl from blood. Ethacrynic acid and furosemide (50 mg/kg IV) reduced by 20-30% the rate of permeation of 36Cl across the blood-CSF barrier, and they elevated [K] and [Cl] in choroid plexus (CP) by 15-25%. The loop diuretic-induced buildup of K and Cl in CP (lateral and 4th ventricle) was likely a reflection of decreased movement of these ions across the apical membrane into CSF. 36Cl activity in parietal cortex and pons-medulla decreased in treatment with furosemide and ethacrynic acid, due to slowing of Cl transport across blood-brain and/or blood-CSF barriers. Our inhibitory findings in intact rats are consistent with those from previous in vitro experiments demonstrating diminution by loop diuretics of Na, K and Cl transport across isolated CP membranes.

Acetazolamide↗
PubMed1992

Lack of effect of social context on the reinforcing effects of diazepam in humans.

The reinforcing effects of diazepam (DZP) were compared under two conditions in human volunteers using a cumulative dose procedure. Under the social (SOC) condition, groups of two to four subjects participated concurrently whereas in the solitary (SOL) condition subjects participated individually. During the first four sessions of each condition, subjects received 20 mg DZP in five divided doses (4 mg) in two of the sessions and placebo (PL) in the other two sessions. Each drug (DZP or PL) was administered in a distinctively colored capsule and labeled by letter code. During the last three choice sessions, subjects chose which capsule they wished to self-administer and were allowed to choose up to a maximum of seven capsules (28 mg DZP) during each session. Subjects also filled out questionnaires that assessed momentary mood. Overall, DZP was chosen on 33% of choice sessions and there were no differences across conditions. There was a tendency for choice to be correlated with levels of weekly alcohol consumption and liking scores, and as well the latter two measures were correlated. DZP produced sedative-like subjective effects that did not appear to be related to setting, choice of drug in the study, or alcohol drinking history. These results partially confirm previous reports of a relationship between DZP preference and alcohol consumption, but differ from previously reported studies in the overall lower level of DZP choice.

Adult↗
PubMed1992

Craving: consensus of status and agenda for future research.

The term craving is used frequently in relationship to drug abuse and its treatment but there is disagreement over its definition and role. In February 1991, a meeting of experts from several disciplines, sponsored by the Addiction Research Center (ARC) of the National Institute on Drug Abuse, was convened with the goal of reaching consensus about the importance of craving and to suggest a future research program. The participants agreed that craving is a subjective state in humans that is associated with drug dependence but little is known about its determinants, relationship to drug taking, and measurement. To advance our knowledge, a substantial research program is required. The outcome of this research effort could have important consequences for increasing our understanding of the determinants of drug abuse.

Humans↗
PubMed1992

Maturational differences in acetazolamide-altered pH and HCO3 of choroid plexus, cerebrospinal fluid, and brain.

The carbonic anhydrase inhibitor acetazolamide is useful for analyzing ion transport, pH regulation, and fluid formation in developing central nervous system. We used the 14C-labeled dimethadione technique to measure alterations in steady-state pH, and to estimate the HCO3 concentration [HCO3], in choroid plexus (CP), cerebrospinal fluid (CSF), and cerebral cortex of 1- and 3-wk-old Sprague-Dawley rats treated with acetazolamide or probenecid. These drugs can suppress transport of HCO3 and other anions in some cells, consequently altering intracellular pH. In 1-wk-old infant rats whose CSF secretory process is incompletely developed, 1 h of acetazolamide treatment did not significantly change CP intracellular pH or [HCO3]. However, in 3-wk-old rats, in which the ability of CP to secrete ions and fluids is almost fully developed, acetazolamide caused marked increases in CP cell intracellular pH and [HCO3]. In contrast, acetazolamide-induced alkalinization was not observed in CSF or cerebral cortex of the 1- and 3-wk-old animals. The other test agent, probenecid (an inhibitor of anion transport but not of carbonic anhydrase), did not alter the pH of any region at any age investigated. Overall, the results are interpreted in light of developmental changes in carbonic anhydrase and previous findings from kinetic analyses of ion-translocating systems in CP. Acetazolamide may interfere with a CP apical membrane HCO3 extrusion mechanism not fully operational in infant rats.

Acetazolamide↗