Search PubMed⌕ Search

Biomedical subjects

C E Johanson

Publications and source records attributed to C E Johanson.

At least 19 recordsLinked to original sources
PubMed2001

The subjective effects of MDMA and mCPP in moderate MDMA users.

The present study is part of a research program designed to better understand the neurochemical mechanisms underlying the abuse liability of 3,4-methylenedioxymethamphetamine (MDMA) in humans. In these studies, MDMA will be compared to prototypical dopamine (D-amphetamine) and serotonin (meta-chlorophenylpiperazine, mCPP) releasing agents on a variety of measures related to dependence. In order to determine an acceptable dose range (safe but active) of MDMA and mCPP for these studies, moderate MDMA users were administered escalating doses of MDMA (75, 110 and 145 mg/70 kg) and mCPP (17.5, 35 and 52.5 mg/70 kg). Each participant received a single dose under controlled laboratory conditions, i.e. this was a six-group design with a separate group for each dose. There were five participants tested in each group. MDMA increased blood pressure and heart rate whereas mCPP had no effect on these physiological measures. MDMA produced increases in subjective effects indicative of both stimulant (increases in POMS Elation, ARCI Amphetamine, VAS High and Stimulated scale scores) and hallucinogenic effects (increases on five of the six scales of the Hallucinogenic Rating Scale). mCPP produced similar stimulant effects (e.g. increases on POMS Elation, VAS High and Stimulated), as well as hallucinogenic effects (four of the six scales of the Hallucinogenic Rating Scale), which has not been observed in previous studies.

Adolescent↗
PubMed2001

Human choroid plexus growth factors: What are the implications for CSF dynamics in Alzheimer's disease?

The choroid plexus plays a key role in supporting neuronal function by secreting cerebrospinal fluid (CSF) and may be involved in the regulation of various soluble factors. Because the choroid plexus is involved in growth factor secretion as well as CSF dynamics, it is important to understand how growth factors in CSF interact with the brain parenchyma as well as with cells in direct contact with the flowing CSF, i.e., choroid plexus and arachnoid villi. While the existence of growth factors in the choroid plexus has been documented in several animal models, the presence and distribution of growth factors in the human choroid plexus has not been extensively examined. This study describes the general distribution and possible functions of a number of key proteins in the human choroid plexus and arachnoid villi, including basic fibroblast growth factor, FGF receptor, and vascular endothelial growth factor. FGF and VEGF could both be readily demonstrated in choroid plexus epithelial cells. The presence of FGF and VEGF within the choroid plexus was also confirmed by ELISA analysis. Since Alzheimer's disease (AD) is known to be associated with a number of growth factor abnormalities, we examined the choroid plexus and arachnoid villi from AD patients. Immunohistochemical studies revealed the presence of FGF and VEGF within the AD choroid plexus and an increased density of FGFr in both the choroid plexus and the arachnoid villi of AD patients. No qualitative changes in the distribution of FGF and VEGF were observed in the AD choroid plexus. The appearance of FGFr in AD arachnoid was associated with robust amyloid and vimentin immunoreactivity. These findings confirm the presence of FGF and VEGF within the normal and AD choroid plexus and suggest that the alteration of growth factors and their receptors may contribute to the pathogenesis of the hydrocephalus ex vacuo that is characteristically seen in AD.

Alzheimer Disease↗
PubMed2001

Behavioral measurement of thermal pain sensitivity in humans: effects of stimulus intensity and instructions.

This study validated a human behavioral model of thermal nociception analogous to the rodent tail-flick assay. Effects of instructions and stimulus intensity on behavior (i.e., finger withdrawal latency) were evaluated. Using a repeated measures randomized crossover design, the authors exposed 10 volunteers to varying radiant heat intensities (from 42.2 to 52.2 degrees C) during each of four sessions. In the different sessions, participants were told to remove their finger when they felt heat, felt unpleasant, felt pain, or could no longer tolerate pain. Withdrawal latencies significantly decreased as stimulus intensity increased and significantly increased for sensory, affective, pain, and intolerance instructions. Instruction set differences were significantly larger at higher stimulus intensities. This technique may be useful in human psychopharmacological research.

Adolescent↗
PubMed2001

FGF-2 immunoreactivity in adult rat ependyma and choroid plexus: responses to global forebrain ischemia and intraventricular FGF-2.

Fibroblast growth factor 2 (FGF-2) immunoreactivity (IR) was examined in the ependyma and choroid plexus (CP) of lateral and third ventricles in normal adult rats, as well as in response to transient forebrain ischemia (TFI) and exogenous FGF-2 delivered intraventricularly for several days by osmotic pump. Similar patterns of FGF-2 IR were seen in the CP epithelia of both lateral and third ventricles, as well as in ependymal cells of the third ventricle and along lateral sides of the lateral ventricles. Consistent staining was seen along the apical aspect of epithelial cells facing the cerebrospinal fluid (CSF). Cytoplasmic staining was seen in the absence of ischemia, and was dramatically reduced in response to TFI. FGF-2 treatment followed by TFI resulted in sustained FGF-2 IR within CP and ependymal cells, supporting the idea that these tissues are involved in synthesis and secretion of growth factors into the CSF. In contrast, along the medial sides of the lateral ventricles, adjacent to brain structures such as the hippocampus, consistent staining was seen along the basal aspect of the ependymal cells. We propose that at least some regions of ependyma may function to transport molecules such as FGF-2 directly into the underlying brain parenchyma.

Animals↗
PubMed2000

Buprenorphine-induced changes in mu-opioid receptor availability in male heroin-dependent volunteers: a preliminary study.

A principle of opioid pharmacotherapy is that high medication doses should occupy fractionally more opioid receptors that mediate heroin effects. In this preliminary study we examined in vivo mu opioid receptor (muOR) binding in three healthy opioid-dependent volunteers during maintenance on 2 and 16 mg sublingual buprenorphine (BUP) liquid, and after detoxification (0 mg) under double-blind, placebo-controlled conditions, and once in matched controls. Binding measures were obtained with the muOR-selective radioligand [11C]carfentanil (CFN) and PET 4 hrs after BUP administration. BUP induced dose-dependent reductions in muOR availability, 36-50% at 2 mg and 79-95% at 16 mg relative to placebo. Heroin abusers also had greater muOR binding potential in the inferofrontal cortex and anterior cingulate regions during placebo, compared to matched controls. Further studies are warranted to examine the relationship of muOR availability with BUP therapeutic actions, and the clinical implications of increased muOR binding during withdrawal.

Adult↗
PubMed2000

Choroid plexus recovery after transient forebrain ischemia: role of growth factors and other repair mechanisms.

1. Transient forebrain ischemia in adult rats, induced by 10 min of bilateral carotid occlusion and an arterial hypotension of 40 mmHg, caused substantial damage not only to CA-1 neurons in hippocampus but also to epithelial cells in lateral ventricle choroid plexus. 2. When transient forebrain ischemia was followed by reperfusion (recovery) intervals of 0 to 12 hr, there was moderate to severe damage to many frond regions of the choroidal epithelium. In some areas, epithelial debris was sloughed into cerebrospinal fluid (CSF). Although some epithelial cells were disrupted and necrotic, their neighbors exhibited normal morphology. This patchy response to ischemia was probably due to regional differences in reperfusion or cellular metabolism. 3. Between 12 and 24 hr postischemia, there was marked restoration of the Na+, K+, water content, and ultrastructure of the choroid plexus epithelium. Since there was no microscopical evidence for mitosis, we postulate that healthy epithelial cells either were compressed together on the villus or migrated from the choroid plexus stalk to more distal regions, in order to "fill in gaps" along the basal lamina caused by necrotic epithelial cell disintegration. 4. Epithelial cells of mammalian choroid plexus synthesize and secrete many growth factors and other peptides that are of trophic benefit following injury to regions of the cerebroventricular system. For example, several growth factors are upregulated in choroid plexus after ischemic and traumatic insults to the central nervous system. 5. The presence of numerous types of growth factor receptors in choroid plexus allows growth factor mediation of recovery processes by autocrine and paracrine mechanisms. 6. The capability of choroid plexus after acute ischemia to recover its barrier and CSF formation functions is an important factor in stabilizing brain fluid balance. 7. Moreover, growth factors secreted by choroid plexus into CSF are distributed by diffusion and convection into brain tissue near the ventricular system, e.g., hippocampus. By this endocrine-like mechanism, growth factors are conveyed throughout the choroid plexus-CSF-brain nexus and can consequently promote repair of ischemia-damaged tissue in the ventricular wall and underlying brain.

Animals↗
PubMed2000

The influence of exchange delays on cigarette versus money choice: a laboratory analog of voucher-based reinforcement therapy.

Contingency-management interventions that provide reinforcement in the form of exchangeable vouchers, contingent on drug abstinence, are among the most effective substance abuse treatment strategies available. Factors known to contribute to the efficacy of these interventions include voucher magnitude and the schedule with which vouchers are made available. Another potential factor may be the delay between earning a voucher and exchanging it for a desired good or service. The authors adapted a laboratory analog of a voucher program to examine the effects of immediacy of reinforcement and its interaction with reinforcer magnitude. Abstinent cigarette smokers made repeated choices between puffs on a cigarette and points worth a variety of monetary values (10 cents-2 dollars). The time at which these points could be exchanged for money varied from the end of the session to 1 or 3 weeks. Results indicated that longer exchange delays and tower magnitude reinforcers increased the number of choices for drug.

Adult↗
PubMed2000

Discrimination of intranasal cocaine.

In the development of medications for the treatment of cocaine abuse, the drug discrimination paradigm can be used to identify medications that can attenuate the discriminative stimulus effects of cocaine. To ascertain that participants are basing the discrimination on the drug's central effects, this paradigm requires that the drug and placebo administrations do not produce any peripheral effects on which the discrimination can be based. This study examined whether intranasal cocaine (50 mg) can be discriminated from placebo (46 mg lactose + 4 mg cocaine), how quickly this discrimination can be made, and whether pretreatment with intranasal benzocaine can affect this discrimination. Results showed that subjects were generally able to discriminate the drug conditions correctly 15 s after administration, and this was unaffected by benzocaine. These results suggest that subjects base the discrimination on peripheral drug effects (e.g. taste) that are not affected by anaesthesia of the nasal passage, and that the intranasal route of cocaine administration is unlikely to be feasible with a drug discrimination paradigm.

Administration, Intranasal↗
PubMed1999

Opioid reinforcement in heroin-dependent volunteers during outpatient buprenorphine maintenance.

This study examined the reinforcing effects of hydromorphone (HYD) (0, 4, 8, and 16 mg/70 kg i.m.) in heroin-dependent outpatient volunteers maintained on buprenorphine (BUP) at doses of 2, 4, and 8 mg, each for 2 weeks. Following a week of maintenance at each dose, volunteers received injections of one of the four HYD doses under double-blind conditions. Eight volunteers (abstainers) were heroin-free during HYD test weeks, whereas six volunteers remained heroin-positive (nonabstainers). Among abstainers, HYD had minimal reinforcing value, whereas in nonabstainers there were marked dose-related increases in HYD reinforcing value, which were not attenuated by increasing doses of BUP. A similar pattern was found for HYD subjective agonist effects. Heroin craving among nonabstainers was significantly higher compared with abstainers, and was reduced in a dose-related manner by HYD. Although BUP and HYD produced dose-related miosis, abstinence status had no differential effect. In summary, BUP effects on opioid reinforcement were consistent from outpatient setting (heroin abstinence) to laboratory setting (decreased HYD reinforcement), supporting the validity of this laboratory model.

Adult↗
PubMed1999

Pharmacokinetic comparison of the buprenorphine sublingual liquid and tablet.

Buprenorphine is a mu opioid partial agonist being developed as a treatment for opioid dependence. Buprenorphine, usually administered as a sublingual liquid, is now being developed as a sublingual tablet for clinical use. The present study compared participants' plasma concentrations after daily maintenance on three buprenorphine liquid doses (2, 4 and 8 mg) and one tablet dose (8 mg). Fourteen opioid-dependent individuals (11 males, three females) participated. Plasma samples were collected over a 24-h period after at least 7 days of maintenance on each dose. Results showed that the liquid doses produced dose-related increases in plasma concentrations. The 8-mg tablet produced mean plasma concentrations significantly lower than those of the 8-mg liquid, although there was substantial individual variability. Thus, the buprenorphine tablet dose might have to be adjusted to produce plasma concentrations equivalent to those of the liquid.

Administration, Sublingual↗
PubMed1999

Angiotensin II regulates choroid plexus blood flow by interacting with the sympathetic nervous system and nitric oxide.

Blood flow to the rat choroid plexus has minimal variability when plasma angiotensin II (AII) concentration is changed within a broad range of levels. We tested the hypothesis that a complex interplay of the vasoconstrictor and vasodilator AII actions in choroidal tissue results in small net changes in choroidal blood flow. Blood flow was measured with 123I- or 125I-N-isopropyl-p-iodoamphetamine. AII was infused intravenously (i.v.) at 30 (moderate dose) and 300 ng kg-1 min-1 (high dose), which respectively decreased (15%) and did not change choroidal blood flow. To determine whether AII regulates choroidal blood flow by interacting with the sympathetic nervous system, rats were given phentolamine (1 mg kg-1, i.v.). This alpha-adrenoceptor antagonist by itself did not alter blood flow; however, it attenuated the blood flow-lowering effect of moderate AII dose. Phentolamine also unmasked the vasodilator AII actions at high peptide concentration. beta-Adrenoceptor blockade, with propranolol (1 mg kg-1, i.v.), reduced blood flow (18-20%) and increased vascular resistance (23-26%). During beta-adrenoceptor blockade, a further decrease in blood flow (15-21%) and increase in vascular resistance (23%) was noted when high AII dose was administered. The direct vasoconstrictor effect of AII at moderate dose on choroidal vasculature was examined in rats subjected to chronic bilateral superior cervical ganglionectomy. In these animals, AII decreased blood flow (24%) and increased vascular resistance (24%). To find out whether the hemodynamic AII actions in choroidal tissue are mediated by nitric oxide (NO), Nomega-nitro-l-arginine methyl ester (l-NAME) was used. l-NAME (0.1 mg kg-1, i.v.) by itself did not alter blood flow; however, in l-NAME-treated rats high AII dose lowered blood flow (25-32%) and increased vascular resistance (30-43%). We conclude that the vasoconstrictor AII actions involve a direct peptide effect on the choroidal vascular bed, and the AII-mediated potentiation of sympathetic activity, which results in the activation of alpha-adrenoceptors. The AII-mediated stimulation of sympathetic nerves also results in the beta-adrenoceptor-dependent relaxation of choroidal blood vessels. In addition, choroidal vasodilatory actions of AII are NO-mediated.

Adrenergic alpha-Antagonists↗
PubMed1999

The effects of cocaine on mood and sleep in cocaine-dependent males.

The effects of cocaine use and withdrawal on mood and sleep were examined. Three cocaine-dependent men lived in an inpatient facility for approximately 4 weeks, which included an initial abstinence phase (8-10 days), a cocaine administration phase (5 days), and a 2nd abstinence phase (14-16 days). During the 2nd phase, cocaine was administered intranasally a few hours before bedtime. During the day, mood and daytime sleepiness were measured, and sleep was monitored each night. Cocaine produced typical changes in mood and blood pressure, and sleep was severely disrupted. Following Phase 2, there were no changes in mood that was indicative of an abstinence syndrome, although, initially, daytime sleepiness increased. After 2 weeks, sleep architecture remained different from age-matched controls. This study is the first to measure changes in sleep architecture polysomnographically following a period of controlled cocaine use.

Administration, Inhalation↗
PubMed1999

AVP V1 receptor-mediated decrease in Cl- efflux and increase in dark cell number in choroid plexus epithelium.

The cerebrospinal fluid (CSF)-generating choroid plexus (CP) has many V1 binding sites for arginine vasopressin (AVP). AVP decreases CSF formation rate and choroidal blood flow, but little is known about how AVP alters ion transport across the blood-CSF barrier. Adult rat lateral ventricle CP was loaded with 36Cl-, exposed to AVP for 20 min, and then placed in isotope-free artificial CSF to measure release of 36Cl-. Effect of AVP at 10(-12) to 10(-7) M on the Cl- efflux rate coefficient (in s-1) was quantified. Maximal inhibition (by 20%) of Cl- extrusion at 10(-9) M AVP was prevented by the V1 receptor antagonist [beta-mercapto-beta, beta-cyclopentamethyleneproprionyl1,O-Me-Tyr2,Arg8]vasopressin. AVP also increased by more than twofold the number of dark and possibly dehydrated but otherwise morphologically normal choroid epithelial cells in adult CP. The V1 receptor antagonist prevented this AVP-induced increment in dark cell frequency. In infant rats (1 wk) with incomplete CSF secretory ability, 10(-9) M AVP altered neither Cl- efflux nor dark cell frequency. The ability of AVP to elicit functional and structural changes in adult, but not infant, CP epithelium is discussed in regard to ion transport, CSF secretion, intracranial pressure, and hydrocephalus.

Animals↗
PubMed1999

Altered formation and bulk absorption of cerebrospinal fluid in FGF-2-induced hydrocephalus.

Upregulation of certain growth factors in the central nervous system can alter brain fluid dynamics. Hydrocephalus was produced in adult Sprague-Dawley rats by infusing recombinant basic fibroblast growth factor (FGF-2) at 1 microg/day into a lateral ventricle for 2, 3, 5, or 10-12 days. Lateral and third ventricular enlargement progressively increased from 2 to 10 days. Ventriculomegaly was also induced by a 75% reduced dose of FGF-2. At 10-12 days, there was a 29% attenuation in cerebrospinal fluid (CSF) formation rate, from 2. 5 to 1.8 microliter/min (P < 0.01). Choroid plexus, the main site of CSF secretion, had an augmented number of dark epithelial cells, which have previously been associated with decreased choroidal fluid formation. The twofold elevated resistance to CSF absorption, i.e., 0.8 to 1.7 mmHg. min(-1). microliter(-1), was attributable, at least in part, to enhanced fibrosis and collagen deposits in the arachnoid villi, a major site for CSF absorption. Normal CSF pressure (2-3 mmHg) was consistent with a patent cerebral aqueduct and reduced CSF formation rate. The FGF-2-induced ventriculomegaly is interpreted as an ex vacuuo hydrocephalus brought about by an altered neuropil and interstitium of the brain.

Absorption↗
PubMed1998

Vasopressin mediates the inhibitory effect of central angiotensin II on cerebrospinal fluid formation.

Angiotensin II infused at low doses into the cerebral ventricles decreases cerebrospinal fluid (CSF) production. Since central angiotensin II also activates the sympathetic nervous system and promotes vasopressin release, the roles of these two factors in mediating the inhibitory effect of angiotensin II on CSF formation were studied. CSF production was measured in rats by the ventriculocisternal perfusion method. During central angiotensin II infusion (5 pg min(-1)), the following adrenoceptor antagonists were administered intravenously (i.v.): phentolamine (alpha1/alpha2, 2 mg/kg per h), prazosin (alpha1, 1 mg/kg per h), and propranolol (beta, 1 mg/kg per h). None of these agents affected the inhibitory effect of angiotensin II on CSF formation. In comparison, in animals administered i.v., the vasopressin V1 receptor antagonist, d(CH2)5Tyr(Me)Arg-vasopressin (10 microg/kg per h), the angiotensin II-induced decrease in CSF production was abolished. Our observations indicate, therefore, that vasopressin mediates the inhibitory effect of central angiotensin II on CSF formation.

Adrenergic Antagonists↗