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Biomedical subjects

C E Johanson

Publications and source records attributed to C E Johanson.

At least 91 records · Page 5Linked to original sources
PubMed1989

Assessing pentobarbital preference in normal volunteers using a cumulative dosing procedure.

Preference for pentobarbital was assessed in 12 normal healthy volunteers using a seven-session cumulative dosing choice procedure. On the first four sessions subjects sampled the drug and a placebo, and on the last three sessions they chose the substance they preferred. During each of the sampling sessions they ingested, at 30-min intervals, five capsules containing either pentobarbital (30 mg per dose) or placebo. During the choice sessions subjects first chose which capsules they preferred to take (drug or placebo), and then took from one to seven of these capsules, separated by 30 min between ingestions. Self-report measures of subjective effects were obtained at regular intervals during each session. Subjects chose the pentobarbital-containing capsules on average 52% of choice sessions, and ingested an average total dose of 132 mg. Although the drug produced only modest, sedative-like subjective and behavioral effects and there was little evidence of euphoric effects in the group as a whole, individual differences in drug liking and choice were observed. The results are discussed in terms of variables that affect the reinforcing effects of pentobarbital in normal volunteers, and they are contrasted to previous findings using this procedure with other sedative drugs.

Adult↗
PubMed1989

Reinforcing and subjective effects of diazepam in nondrug-abusing volunteers.

Preference for diazepam was assessed in 18 light and 12 moderate social drinkers using a cumulative dosing procedure. The 7-session procedure consisted of: 1) four sampling sessions, during which participants ingested color-coded capsules containing either diazepam (five 4-mg capsules administered at 30-min intervals; total dose 20 mg) or placebo, and 2) three choice sessions, during which they could ingest up to 7 capsules of their preferred color of capsule, each separated by 30 min. Subjective (mood) and behavioral (performance) measures were obtained throughout the 4-hour sessions. The light social drinkers chose diazepam over placebo on 66% of the choice sessions, and ingested a mean dose per session of about 16 mg. The moderate drinkers chose diazepam on 100% of the choice sessions, and ingested an average dose of 25 mg per session. Diazepam produced sedation in both groups, but in the moderate drinkers it also increased measures of subjective effects suggestive of "euphoria." The results indicate that diazepam can serve as a positive reinforcer under laboratory conditions in nondrug-abusing individuals who are moderate users of alcohol and other drugs. Greater reinforcing efficacy may be indicative of higher risk of abuse. The results illustrate the usefulness of the cumulative dosing procedure to measure both drug preference and dose preference.

Adult↗
PubMed1989

Acidosis, acetazolamide, and amiloride: effects on 22Na transfer across the blood-brain and blood-CSF barriers.

Sprague-Dawley rats were given treatments, known to decrease 22Na movement into choroid plexus and CSF, to investigate their effect on 22Na transfer across the cerebral capillaries. Acidic salts, acetazolamide, or amiloride was injected intraperitoneally into bilaterally nephrectomized rats, and the rate of 22Na uptake into parietal cortex, pons-medulla, and CSF was determined at 12, 18, and 24 min. Severe acidosis (arterial pH 7.2), produced by HCl injection, decreased the rate of 22Na entry into both brain regions and CSF by 25%, whereas mild acidosis (pH 7.3) from NH4Cl injection reduced brain entry by 18%, but CSF entry by only 10%. Like HCl acidosis, amiloride reduced transport into both brain and CSF by 22%. Penetration of 22Na into parietal cortex was unchanged by acetazolamide, but that into CSF was slowed 30%. Since uptake of 22Na into cortical regions is primarily movement of tracer across the cerebral capillaries when tracer uptake time is less than 30 min, the results indicate that both metabolic acidosis and amiloride decrease Na+ permeativity at the cerebral capillaries as well as at the choroid plexus. Acetazolamide, on the other hand, alters Na+ movement only across the choroidal epithelium.

Acetazolamide↗
PubMed1989

Development of potassium transport capability by choroid plexus of infant rats.

Developmental maturation of K transport and Na+-K+-adenosinetriphosphatase (ATPase) function in the choroid plexus (CP) was investigated in infant rats. K fluxes (86Rb), Na+-K+-ATPase enzyme activities, and [3H]ouabain binding were measured in isolated, lateral CPs removed from anesthetized Sprague-Dawley rats of several ages ranging from 1 day to 6 wk. Morphological integrity of incubated tissue was confirmed by electron microscopy. CP epithelia accumulated K at a lower level during the 1st wk after birth (40 nmol/mg wet wt) compared with CP from rats aged 11-28 days (56 nmol/mg wet wt). However, efflux curves and efflux rate coefficients among the age groups were similar. Both Na+-K+-ATPase activity in CP tissue homogenates and [3H]ouabain binding to isolated CP began to increase between age 10 and 14 days. It is concluded that CP Na+-K+-ATPase has limited capacity in the lateral CP of neonatal rats but that this important transport function matures rapidly in the 1st 2-3 wk after birth.

Aging↗
PubMed1989

Discriminative stimulus properties of midazolam in the pigeon.

Five pigeons were trained to discriminate injections of midazolam (1.0 or 3.0 mg/kg i.m.) from saline with responding maintained under a fixed-ratio 30 schedule of food delivery. When other benzodiazepines were tested, they consistently produced greater than 80% of midazolam-appropriate responding. The order of potency for substituting for midazolam was triazolam greater than alprazolam = diazepam = lorazepam greater than midazolam greater than flurazepam = nitrazepam greater than nordiazepam. The barbiturate phenobarbital (10-100 mg/kg) substituted for midazolam in three of four pigeons whereas pentobarbital (1.0-30 mg/kg) substituted in only two of five pigeons. Several nonbenzodiazepine anxiolytics were also evaluated. Methaqualone (3.0-56 mg/kg) substituted in only one of four pigeons and meprobamate (30-100 mg/kg) failed to substitute in any pigeon tested. CL 218,872, when administered either i.m. (0.3-30 mg/kg) or p.o. (1.0-56 mg/kg), and buspirone (0.3-30 mg/kg) did not substitute for midazolam. Compounds from pharmacological classes not related to midazolam also failed to substitute for midazolam. Pretreatment with the benzodiazepine antagonist flumazenil (Ro 15-1788; 0.03-1.0 mg/kg) antagonized the discriminative stimulus properties of midazolam in a dose-related manner in all pigeons tested. However, this antagonism could not be overcome with increasing doses of midazolam in all pigeons. The results of the present study demonstrate that midazolam is an effective discriminative stimulus in the pigeon. Benzodiazepine anxiolytics, but not other compounds with sedative and/or anxiolytic properties, were found to reliably substitute for midazolam. These results suggest that the discriminative stimulus effects of midazolam are pharmacologically selective.

Animals↗
PubMed1989

Discriminative stimulus properties of histamine H1-antagonists in animals trained to discriminate d-amphetamine or pentobarbital.

Pigeons were trained to discriminate i.m. administered d-amphetamine (AMPH) or pentobarbital (PB) from saline with responding maintained under a fixed-ratio 30 schedule of food delivery. Rhesus monkeys were trained to discriminate intragastrically administered AMPH or PB from saline using a signaled shock-avoidance trial procedure. In AMPH-trained pigeons the histamine H1-antagonists tripelennamine, diphenhydramine and chlorpheniramine consistently produced greater than 80% AMPH-appropriate responding. Pyrilamine substituted for AMPH in two of three pigeons. In contrast, chlorcyclizine, hydroxyzine, promethazine and the histamine H2-antagonist cimetidine all failed to produce AMPH-appropriate responding. None of the histamine H1-antagonists tested substituted for PB in PB-trained pigeons. In AMPH-trained monkeys, only tripelennamine completely substituted for AMPH. Whereas chlorpheniramine, diphenhydramine and pyrilamine did not produce AMPH-appropriate responding in monkeys, these compounds did produce observable excitation and convulsions. As with the PB-trained pigeons, none of the histamine H1-antagonists tested substituted for PB in monkeys. The results of the present study demonstrate that histamine H1-antagonists have differential discriminative stimulus properties in both pigeons and monkeys. Specifically, histamine H1-antagonists known to produce more central nervous system stimulation in humans share discriminative stimulus properties with AMPH and/or produce observable signs of stimulation in monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Regulation of pH and HCO3 in brain and CSF of the developing mammalian central nervous system.

Acute (2-h) metabolic acidosis or alkalosis was induced in immature rats to ascertain the ability of their incompletely-developed CNS to regulate pH when challenged with perturbations in blood [H] and [HCO3]. Brain and cisternal CSF pH were determined from steady-state distribution of [14C]dimethadione, a weak organic acid. By 1 week post partum, there was a remarkable stability of pH in the cerebral cortex of animals subjected to arterial pH extremes of 7.1 and 7.5. However, CSF pH in 1-week-old animals rendered alkalotic remained 0.07-0.08 units above control due to lack of a compensatory increase in pCO2, and to a blood-CSF barrier apparently more permeable to HCO3. As arterial HCO3, i.e. [HCO3]art, was varied from about 10 to 30 mmol/l, the infants maintained [HCO3]csf only half as effectively as adults, i.e. delta [HCO3]art was 0.4 and 0.2 at 1 and greater than 4 weeks, respectively. Throughout postnatal ontogenesis, [HCO3]csf was more resistant to alteration by metabolic acidosis than by alkalosis. Overall, the results indicate that immature rats challenged with systemic acid-base loads are less capable than adults in regulating CSF pH, but they are able to maintain brain pH.

Acidosis↗
PubMed1988

Relationship between the discriminative stimulus properties and subjective effects of drugs.

Behavioral pharmacologists have assumed that the properties of drugs that mediate their discriminative stimulus effects are related to aspects of drug actions that result in their subjective effects in humans. The basis of this assumption is examined in this chapter. Evidence to support this assumption includes the formal properties of the learning process involved in acquiring both behaviors. Although the procedures used to train animals to learn a drug discrimination are explicit, an analysis of how humans learn to attach verbal responses to unobservable internal subjective states appears to involve a similar learning paradigm. Additional evidence of the commonality of the two effects is that the results from drug discrimination studies in animals and studies evaluating subjective effects in humans yield similar drug classifications. However, when subjective drug effects are analyzed in more detail, it is clear that the concordance between the two approaches is not always good. On the other hand, when drug discrimination and subjective effects are both measured in humans, an examination of the results generated when individuals respond differently to the same drug indicates that the hypothesis that their discrimination is based upon a profile of subjective effects is supported.

Animals↗
PubMed1988

Discriminative stimulus and subjective effects of smoked marijuana in humans.

The discriminative stimulus (DS) effects of smoked marijuana were studied by training marijuana smokers to discriminate between the effects of marijuana containing 2.7% delta 9-THC (M) and marijuana containing 0.0% delta 9-THC (P). In addition to measures of discrimination responding, subjective effects were assessed with standardized mood questionnaires. The post-smoking increase in expired air carbon monoxide (CO) level was used as an index of smoke inhalation. Relative to P cigarettes, M cigarettes increased heart rate and produced changes on eight mood scales. M cigarettes were rated as harsher and more potent than P cigarettes, and produced lower levels of CO than P cigarettes. The P--M discrimination was readily acquired by most subjects. The DS effects of marijuana showed a rapid onset, appearing within 90 s from the beginning of smoking. The DS effects were dose dependent, with 0.9% delta 9-THC marijuana producing primarily placebo-appropriate discrimination responding, and 1.4% delta 9-THC marijuana producing 100% drug-appropriate responding. This experimental paradigm could be used to determine whether the DS effects of smoked marijuana would generalize to those of other psychoactive drugs.

Adolescent↗
PubMed1988

Phenylpropanolamine: reinforcing and subjective effects in normal human volunteers.

The reinforcing and subjective effects of phenylpropanolamine (PPA, 25 and 75 mg, PO) were compared with those of d-amphetamine (AMP, 5 mg) in a group of normal, healthy adults (eight males, nine females) with no history of drug abuse. A discrete-trial choice procedure was used in which subjects first sampled placebo and a dose of one of the drugs. Subjects were then allowed to choose between self-administration of drug or placebo on three separate occasions. The relative frequency with which active drug was chosen over placebo was used as the primary index of the drug's reinforcing efficacy. Subjective effects were measured with the Profile of Mood States, a short version of the Addiction Research Center Inventory and a series of visual analog scales. Ratings of drug liking, drug labelling, general activity level and strength of drug preference were also obtained. As expected, AMP was chosen significantly more often than expected by chance (69% of occasions). AMP also increased ratings of drug liking, preference strength, and activity level, and produced a profile of subjective effects consistent with its well-established stimulant and euphorigenic properties. The low dose of PPA was without effect on most measures. PPA 75 mg was chosen significantly less often than expected by chance (39% of occasions). This dose of PPA was most frequently labelled as a stimulant, and produced significant increases on ratings of Anxiety and "stimulated," and decreases on ratings of "sedated" and "hungry." Unlike AMP, PPA did not affect ratings of drug liking or mood scales reflecting euphoria. In sum, these results indicate that PPA does not possess AMP-like dependence potential.

Adult↗
PubMed1988

Discriminative stimulus effects of caffeine and benzphetamine in amphetamine-trained volunteers.

The discriminative stimulus (DS) and subjective effects of caffeine (100 and 300 mg, PO) and benzphetamine (12.5 and 50 mg, PO) were studied in 18 normal human volunteers trained to discriminate between d-amphetamine (10 mg) and placebo. d-Amphetamine increased ratings of drug liking and activity level and produced a profile of subjective effects characteristic of amphetamine and related psychomotor stimulants. The DS effects of d-amphetamine generalized only partially to caffeine and benzphetamine; mean percent d-amphetamine-appropriate responding was 42 and 58 after 100 and 300 mg caffeine, respectively, and 17 and 56 after 12.5 and 50 mg benzphetamine, respectively. Neither dose of caffeine affected ratings of drug liking or activity level, but 300 mg caffeine did produce a profile of subjective effects that partially overlapped with that produced by d-amphetamine. Benzphetamine 50 mg, but not 12.5 mg, increased ratings of drug liking and activity level and produced a profile of subjective effects qualitatively similar to, but weaker than, that produced by d-amphetamine. For both caffeine and benzphetamine, a close relationship was observed between their subjective effects and their ability to substitute for the DS effects of d-amphetamine. These results correspond well with findings obtained from similar studies conducted with laboratory animals, providing further support for the reliability and validity of human drug discrimination paradigms.

Adult↗
PubMed1988

A cumulative dosing procedure for administering marijuana smoke to humans.

Subjective, behavioral and physiological effects of smoked marijuana were measured with a cumulative dosing procedure which allowed dose-related effects to be determined within a single experimental session. Five male and three female occasional marijuana smokers participated. Unit doses of marijuana smoke were administered in a standardized manner on four occasions during each session, each occasion spaced 20 minutes apart. This procedure resulted in a cumulative dose of active (1.4%-THC) marijuana of 0, 2, 4 and 8 puffs after the four successive smoking occasions, respectively. Dependent variables were measured after each smoking occasion. Smoke absorption was monitored by measuring expired air carbon monoxide levels. Subjects participated in three identical sessions spaced a week apart in order to assess the reliability of the procedure. During a fourth session, only placebo (0.0%-THC) marijuana was administered throughout the session as a control. Significant linear dose-effect functions were obtained on several measures, with good session-to-session replicability of most effects. The results demonstrate the feasibility of using a cumulative dosing procedure to evaluate dose-related effects of smoked marijuana in humans. The procedure would be especially useful for the assessment of shifts in dose-effect curves as a result of various experimental manipulations.

Adolescent↗
PubMed1988

The nature of the scheduled reinforcer and adjunctive drinking in nondeprived rhesus monkeys.

Adjunctive drinking was generated in three free-feeding rhesus monkeys by the contingent and intermittent delivery of flavored pellets. The amount of drinking generated was greater when pellet availability was restricted under fixed-interval schedules compared to a massed-reinforcer control condition. The volume of water consumed depended upon the fixed-interval of pellet delivery (FI 180 sec to FI 1800 sec). Peak amounts of water consumed ranged from 532 ml to 650 ml during the 2 hr sessions and the schedule which generated the most drinking was either FI 420 or FI 600 sec, across monkeys. Variables which did not appear to influence the amount of drinking generated within the session were the amount of water consumed outside the session, the rates of responding maintained by pellet delivery and the pattern of responding for pellet delivery. However, when either cocaine or diazepam was the scheduled reinforcer, these same free-feeding monkeys did not engage in adjunctive drinking. The ability of cocaine and diazepam to generate adjunctive drinking was determined first by gradually decreasing the frequency of pellet delivery while keeping drug delivery constant using a second-order schedule of pellet delivery [FR n(FI 300 sec: drug delivery) with n ranging from 1 to 6]. Second, a range of drug doses was tested under a FI 300 sec schedule (cocaine: 0.01-0.3 mg/kg/injection; diazepam: 0.01-0.56 mg/kg/injection). These results suggest that there may be some restriction on the generation of adjunctive drinking depending upon the nature of the scheduled reinforcer.

Animals↗
PubMed1988

Oral ethanol self-administration in free-feeding rhesus monkeys.

The ability of a conditioning procedure to establish oral ethanol self-administration in free-feeding rhesus monkeys was assessed. The conditioning procedure required the monkey to drink an ethanol solution in order to have access to a sweet orange-flavored solution. Following an average of 14 sessions under these conditions, the orange solution was no longer delivered and ethanol solution alone was made available in the sessions. During both the conditioning and the ethanol self-administration portions of the experiment each monkey was required to drink an average of 0.5 g/kg ethanol per session in order to continue in the experiment. Of the nine monkeys exposed to these contingencies, five monkeys continued to self-administer ethanol after the presentation of the orange drink was discontinued. However, two of these five monkeys decreased their ethanol solution intake below 0.5 g/kg within 3 weeks after the conditioning sessions had terminated. The three monkeys that sustained high ethanol intake were male and had histories of drug self-administration, suggesting that gender and drug history may influence the initiation of ethanol self-administration. Once ethanol self-administration was established, concentrations of ethanol from 4 to 15% (v/v) were made available. The monkeys consumed intoxicating amounts of ethanol, as indicated by average intakes ranging from 0.5 to 0.9 g/kg and blood ethanol levels over 100 mg/dl. These results demonstrate that ethanol self-administration can be established and maintained through the initial reinforcement of ethanol consumption by the contingent presentation of another reinforcing stimulus. However, the results of this study also indicate that individual differences may be an important determinant of animals initiating ethanol self-administration.

Alcohol Drinking↗