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Biomedical subjects

C E Johanson

Publications and source records attributed to C E Johanson.

At least 19 recordsLinked to original sources

The effects of methamphetamine on fine motor control in rhesus monkeys.

Six rhesus monkeys were trained to extend their arms through a tube to press a lever with between 25 and 40 g of force for 3 or 5 sec. Responding was maintained by the delivery of 1.5 cc of water. Stimulus lights indicated whether the exerted force was below 25 g. between 25 and 40 g (i.e., correct) or above 40 g. Sessions were terminated after 50 water deliveries or 30 min had elapsed. Performance was well-maintained in all monkeys. Allowing the animals access to water prior to the session had no effect on performance. Discontinuing sessions for two weeks disrupted some aspects of performance but responding improved within 5 sessions. Single injections of methamphetamine (0.06-0.5 mg/kg) were given IM 20 min prior to the session. The highest dose of 0.5 mg/kg totally eliminated responding. Lower doses decreased rate of responding somewhat and increased phasic activity (i.e., tremors) in a dose-dependent manner. The procedure seems ideally suited for investigating the effects of psychotropic drugs on fine motor control in rhesus monkeys.

Animals

The sink action of cerebrospinal fluid in uremia.

The distribution of water, electrolytes and non-electrolytes in various compartments of the central nervous system was analyzed in rats subjected to various stages of uremia. After bilateral nephrectomy for various periods of time ranging from 1 to 18 h, there is a progressive hyperkalemia, hyponatremia and metabolic acidosis. Although the cerebrospinal fluid (CSF) [K] progressively increases to a concentration of 6 mmol/l at 48 h post-nephrectomy, the ratio of CSF [K]/plasma [K] remains relatively constant throughout the duration of the uremic challenge; on the other hand, the concentration gradient for Na (CSF to plasma) markedly increases with progression of uremia. The steady rise in cellular [K] in both the choroid plexus and in at least one compartment of the cerebral cortex is presumably a reflection of stimulattion of the Na-K pump caused by a build-up in [K] in the extracellular fluids of the brain. The blood-brain and blood-CSF barrier systems to both 14C-urea and 131I remain intact 24--48 h after nephrectomy; and there is not any evidence of cerebral edema at any stage of uremia. Thus, several lines of evidence indicate that the CSF-sink effect is maintained even in advanced uremia.

Acid-Base Equilibrium

Distribution of fluid between extracellular and intracellular compartments in the heart, lungs, liver and spleen of neonatal rats.

The volume of fluid in various tissue compartments of thoracic and abdominal viscera in neonatal rats has been calculated from the steady state distribution of radioindicators. During the first 3 weeks after birth, the volume of extracellular fluid (3H-inulin space) decreases at a similar rate (ca. 0.04 ml/g tissue/week) in heart, lungs, liver and spleen. Over the same postnatal period, the 51Cr tagged erythrocyte space (an estimate of vascularity) remains relatively constant in liver, increases slightly in the heart and spleen, and rises substantially (3-fold increase) in the lungs. The volume of parenchymal cell water, calculated from data for tissue water content and radioindicator spaces, tends to increase with age. However, the distribution of fluid between extracellular and intracellular compartments in 3-week-old animals is similar to that in adults.

Animals

Electric shock delivery system for rhesus monkeys: its effect on escape responding.

The present experiment evaluated a simple chronic electric shock delivery system for rhesus monkeys restrained by a harness and arm arrangement used in experiments involving intravenous drug delivery. Electric shock was delivered via two small electrodes surgically implanted in the lumbar muscle. During experimental sessions, responding on a fixed-ratio 10 schedule terminated the delivery of a train of 100 electric shock pulses and produced a 3 min timeout. A maximum of 19 trials were possible during each daily session. Overall rate of responding increased as electric shock intensity was increased from 0 to 4 mA and the characteristics of responding were similar to previous studies using other systems and species. The results demonstrate that electric shock delivered by the present system is a negative reinforcer. In addition, the system is easy to implant, causes little tissue damage, relatively long-lasting and can be used in experimental situations which involve responding maintained by intravenous drug delivery in rhesus monkeys.

Animals

Uptake of [14C]urea by the in vivo choroid plexus--cerebrospinal fluid--brain system: identification of sites of molecular sieving.

1. The time course of the uptake of [(14)C]urea by the lateral ventricular choroid plexus of the adult rat in vivo was analysed to delineate further the permeability characteristics of the epithelial membrane of this secretory tissue.2. Eight hours after I.P. injection, [(14)C]urea attained a steady-state distribution in 78% of the tissue water of lateral ventricular choroid plexus; similarly, approximately 8 hr was required for radiourea to reach a steady-state concentration in both the cerebral cortex and cerebrospinal fluid (c.s.f.).3. Results obtained for compartment analysis were used to calculate the concentration of [(14)C]urea in the epithelium of the lateral ventricular plexus during the approach to and at steady-state distribution. Even after 1 hr of distribution, the [(14)C]urea concentration in choroid cell water was less than 15% of that in plasma water.4. Although the concentration of radiourea in choroid cell water continually increased after 3 hr, it remained in equilibrium with the concentration of [(14)C]urea in c.s.f. water. At the steady state (i.e., 8 hr), the distribution of [(14)C]urea between the water of plasma and that of the choroidal epithelium was considerably away from equilibrium (i.e., by 25-30%).5. An analysis of the concentration gradients for [(14)C]urea across both the apical (c.s.f.-facing) and basolateral (plasma-facing) membranes of the epithelium of the lateral ventricular plexus suggests that the movement of urea is hindered to a greater extent by the basolateral membrane than by the apical membrane.6. Only a single half-time component (1.3 hr) can be resolved from analysis of the curve describing the time course of uptake of radiourea by the choroid epithelial cell compartment.7. The concentration gradient data suggest that urea penetrates from blood to c.s.f. via the choroid plexus by a transcellular pathway; however, it is not possible to rule out a paracellular pathway for urea movement.8. At the steady state, radiourea distributes into 88% of the water of cerebral cortex. This observation, together with the finding of a steady-state concentration gradient for [(14)C]urea from cortical tissue to c.s.f., constitutes evidence that urea movement is hindered at the blood-brain barrier as well as at the blood-c.s.f. barrier.

Animals

Effects of intravenous cocaine, diethylpropion, d-amphetamine and perphenazine on responding maintained by food delivery and shock avoidance in rhesus monkeys.

The effects of perphenazine, cocaine, diethylpropion and d-amphetamine on responding maintained by both food delivery and electric shock avoidance were determined using a multiple schedule of reinforcement in rhesus monkeys. This schedule had three components, each separated by a timeout: a fixed-ratio schedule of food delivery, a schedule of spaced responding (differential reinforcement of low rates) maintained by food delivery and a fixed-ratio schedule of shock avoidance. Control rates of responding on both ratio schedules were similar and were high relative to the low rates generated by the schedule of spaced responding. Perphenazine decreased rates on all three schedules in a dose-dependent fashion. All three psychomotor stimulants decreased food-maintained ratio responding at doses which had little effect on or increased rates of shock avoidance. Except for diethylpropion and d-amphetamine in one animal in which rates were increased, low rates of spaced responding were also decreased.

Animals

The effects of electric shock on responding maintained by cocaine injections in a choice procedure in the rhesus monkey.

A choice procedure was used to determine the ability of electric shock to suppress cocaine-maintained responding in a situation where cocaine was also available on a second lever without shock. In each session rhesus monkeys were allowed to self-inject cocaine five times in the presence of a stimulus. Thirty minutes after the fifth injection a second dose of cocaine could be self-injected five times in the presence of a different stimulus. At the onset of the injection of this dose a 5 or 10 mA electric shock was delivered. Thirty minutes later choice trials began in which both stimuli were present and monkeys could choose one of the two doses of cocaine. Electric shock was delivered at the onset of the injection of one of these alternatives. Initially, both doses of cocaine were 0.1 mg/kg. The dose of cocaine associated with electric shock was systematically increased until it was preferred to the dose not associated with electric shock. The results indicate that although responding maintained by cocaine can be suppressed by punishment, this effect can be attenuated by increasing magnitude of reinforcement.

Animals

Developmental studies of the compartmentalization of water and electrolytes in the choroid plexus of the neonatal rat brain.

Rats of various postnatal ages were utilized to study developmental changes in the distribution of Na, K and H2O between the various compartments of the lateral ventricular plexus (LVP). During the 3 weeks after birth, as the LVP grows from 0.5 to 0.8 mg, there is a significant increase in plexus K which is accompanied by a progressive decrease in Na and H2O. Also, during this postnatal period the decrease in [3h]inulin space in the plexus is proportional to the decrease in the Na space. Between 3 weeks and adulthood, the [3h]inulin and Na spaces are both augmented to a similar extent; moreover, during this same period of development there is a trebling of the residual [51cr]erythrocyte volume. Despite the substantial changes in the volume of the extracellular fluid and of the residual blood in the plexus with age, the calculated concentrations (mEquiv./kg H2O) of choroid cell Na (30-35) and K (145-155) are similar for all ages investigated. The derived data for cellular ionic concentration, together with the analysis of the ionic concentration gradients (cerebrospinal fluid/plasma H2O), suggest that the transport mechanism which translocates Na and K across the choroidal membrane is operative as early as 3-4 days postnatal. The important role of the choroid plexus in central nervous system homeostasis is discussed in relation to the developing brain.

Age Factors

The effects of perphenazine on self-administration behavior.

In Experiment 1.6 rhesus monkeys prepared with intravenous catheters responded on a fixed-ratio 10 schedule for either an injection of 0.2 mg/kg of cocaine or 0.5 mg/kg of pentobarbital during a daily 3 hr session. The substitution of saline or various doses of perphenazine resulted in very low rates of responding. These results indicate that perphenazine is not a positive reinforcer. Pretreating animals maintained on 0.1 mg/kg or 0.2 mg/kg of cocaine with perphenazine resulted in increases in rate of self-administration at some doses and a decrease in rate at higher doses. The dose of perphenazine which resulted in the maximal increase in cocaine self-administration was directly related to the dose of cocaine maintaining responding. Pretreating animals maintained on 0.5 mg/kg of pentobarbital with perphenazine had no effect at doses which increased cocaine self-administration but decreased rate of pentobarbital self-administration at higher doses. These results indicate that perphenazine is capable of antagonizing some of the effects of cocaine.

Animals

Self-administration of psychomotor stimulant drugs: the effects of unlimited access.

Rhesus monkeys surgically prepared with intravenous catheters were given 23 hr daily access to injection of either cocaine, d-amphetamine, 1-amphetamine, d-methamphetamine or diethylpropion on a fixed ratio 1 schedule of reinforcement for a maximum of 30 days. Responding was maintained by all these drugs but showed both day-to-day and hour-to-hour variability. The two animals self-administering 0.2 mg/kg/infusion cocaine died in less than 5 days. All 6 animals given access to 0.05 mg/kg/infusion d-amphetamine or 0.025 mg/kg/infusion d-methamphetamine also died, but tended to survive more days than animals exposed to cocaine. Three of the 5 animals whose responding was maintained by 0.5 mg/kg/infusion diethylpropion and one of the two animals whose responding was maintained by 0.05 mg/kg/infusion 1-amphetamine survived the entire 30 days despite high rates of intake. Food intake was initially decreased, but often returned to predrug levels and was not related to level of drug intake.

Amphetamine

A choice procedure for drug reinforcers: cocaine and methylphenidate in the rhesus monkey.

A choice procedure was developed to compare the reinforcing efficacy of drug solutions delivered via intravenous catheters to rhesus monkeys. Choices were arranged between doses of cocaine or methylphenidate and saline, different doses of the same drug and doses of both drugs. In each session, monkeys were allowed to self-inject one solution five times in the presence of a stimulus. Thirty minutes after the fifth injection, a second solution could be self-injected five times in the presence of a different stimulus. Thirty minutes later, choice trials began in which both stimuli were present and monkeys could choose one of the two solutions. Rate of responding decreased with increases in dose for both cocaine (0.05-1.5 mg/kg) and methylphenidate (0.075-0.7 mg/kg). Response rates maintained by cocaine were 2 to 3 times higher than those maintained by methylphenidate. Drug was always chosen over saline. Higher doses of cocaine were preferred to lower doses except when both were above 0.5 mg/kg, when no preference was shown. Higher doses of methylphenidate were preferred over low doses, but compared to cocaine, a greater absolute difference between dose magnitude was required to demonstrate preference. When equal doses of cocaine and methylphenidate were compared, no preference was shown. On other comparisons between the drugs, the higher dose was generally preferred regardless of the drug. The reinforcing efficacy of drugs must be considered not only in terms of response rate maintained or reinforcement schedule but also with reference to concurrently available drugs.

Animals