Biomedical subjects
Publications and source records attributed to H Coper.
The study was performed to investigate the influence of ethanol on haloperidol-induced changes of the dopamine (D2) receptors in rat striatal membrane preparations. Subchronic administration of the neuroleptic in the drinking water resulted in an increase of the number of binding sites in a dose-dependent manner. Simultaneous treatment with both haloperidol and ethanol prevented the rise of D2 receptors.
Explore the source record for details and available documents.
Psychostimulants, analeptics, and nootropics are three classes of drugs that have been used with varying success in the treatment of impaired brain functions. They all produce an excitatory and disinhibitory effect on the CNS but can be distinguished through their characteristic properties. Psychostimulants are drugs that lead to a general, but nonphysiological activation, which is followed by a phase of inhibition. Analeptics are drugs that stimulate the CNS, in particular the respiratory and circulatory centers, and which in high doses lead to convulsions. Nootropics are drugs that (in impaired brain functions) lead to a physiological activation of adaptation.
Apomorphine-induced stereotypic behavior was investigated in rats treated with diazepam or haloperidol and with the combination of both drugs in a one day trial or subchronically. The drugs were administered via the drinking water. Diazepam dose-dependently reduced apomorphine stereotypies after the subchronic (6 days) but not after the acute treatment. Haloperidol suppressed apomorphine-induced stereotypic behavior dose-dependently after acute as well as after subchronic administration apparently without the development of tolerance. This discrepancy to other studies may be explained by the concomitant increase in maximum number of D2-receptors in the striatum. The apomorphine antagonistic effect of haloperidol was attenuated when the neuroleptic was administered subchronically in combination with the benzodiazepine. This finding was unexpected since both drugs reduced apomorphine-induced stereotypic behavior when administered alone. The further increase in maximum number of D2-receptors due to combined treatment with low doses of diazepam, suggesting a sort of "over adaptation", possibly explains the haloperidol-antagonistic action of diazepam in the behavioral experiments. Binding studies on dopamine (D1), 5-hydroxytryptamine (5-HT2) and benzodiazepine receptors revealed that modification of the apomorphine-induced stereotypies by the combined treatment with haloperidol and diazepam cannot be explained by interactions of the drugs at the level of the D1, 5-HT2 or benzodiazepine-receptors.
The influence of two antihistamines on the oral intake of various drugs with addictive potency was investigated in rats. Under the chosen conditions neither tripelennamine nor diphenhydramine have reinforcing properties. The reinforcing potency of addictive drugs is not augmented by the both substances. On the contrary, in some cases they led to a decrease in oral intake of the drug solutions offered.
Explore the source record for details and available documents.
Investigations were performed to determine whether the pharmacodynamic effect of barbital, the development of tolerance to or the physical dependence on the hypnotic are responsible for drug-taking behavior. Three groups of male rats, untreated, tolerant to and physically-dependent on barbital, were given free choice between 0.5% barbital solution and tap water. Drug-taking behavior was estimated according to specified criteria. Initially naive rats rejected an unsweetened barbital solution. Tolerant rats also refused the hypnotic, even after they had experienced abstinence symptoms only once. However, tolerant rats that repeatedly underwent withdrawal after an intake of more than 400 mg/kg/day of barbital did show drug taking behavior. Therefore, several experiences with pronounced abstinence symptoms seem to be necessary for initiating and sustaining barbital drug taking behavior in rats.
Four groups of rats were given free choice between water and solutions of either 3 micrograms/ml etonitazene, 5% ethanol (v/v), 0.1 mg/ml diazepam or 3 mg/ml barbital for 10-14 days. With the exception of barbital, some rats spontaneously preferred the drug solutions to water. This preference was reduced by addition of 7 micrograms/ml haolperidol. In a forced drug fluid consumption procedure, the daily administration of 15 mg/kg i.p. of the gamma-aminobutyric acid (GABA)-transaminase blocker aminooxyacetic acid (AOAA) led to a reduction of ethanol and diazepam intake, but not of etonitazene and barbital. It is suggested that the diminished consumption of ethanol and diazepam as caused by GABA-T-inhibition may also be mediated by dopamine which seems to act indirectly, via benzodiazepine receptors and GABA neurons.
The drinking behavior of naive rats changes predictably in a free choice experiment involving water vs. 0.02%, 0.01% and 0.003% (+)-amphetamine solutions: The higher the concentration of the amphetamine solution, the sooner a number of rats quit drinking it, and the less is ingested by those still drinking it. Physically dependent rats having undergone three withdrawals immediately reject (+)-amphetamine solution in a free choice test with water available. The avoidance of withdrawal symptoms does not motivate further self-administration. Therefore, (+)-amphetamine self-administered in drinking water is neither a reinforcer for naive nor for physically dependent rats in sustaining drug taking behavior. In acute and chronic experiments, the transition from increased motor activity to stereotypical behavior could be demonstrated and evidence was produced that tolerance develops to the (+)-amphetamine-induced increase in motor activity.
The effect of the opioid levorphanol on locomotor activity was investigated in rats treated with p-chlorophenylalanine (PCPA) or 6-hydroxydopamine (6-OHDA). Acute oral administration of 10 or 30 mg/kg levorphanol induces a time- and dose-dependent alteration in motility. Ingestion of 10 mg/kg levorphanol in rats with an intact biogenic amine content results in an increase of locomotion for 180 min followed by a longer lasting, small but significant, reduction of motor activity. The course of motility after 30 mg/kg is similar to that after 10 mg/kg, but the initial peak appears after a 3-h delay. In 5-hydroxytryptamine (5-HT)-deficient rats, the first excitation of motility is enhanced and its subsequent depression intensified. After administration 30 mg/kg a general reduction in motor activity occurs. The effect of 10 mg/kg levorphanol after 6-OHDA treatment is on a lower level, similar to that of rats with intact amine content. After 30 mg/kg levorphanol an immediate and longer lasting increase in activity appears. Chronic ingestion of about 40 mg/levorphanol/kg per day enhances the total amount of activity in normal rats as well as in animals with catecholamine (CA) depletion, but not in those treated with PCPA. In all cases, withdrawal of the opioid results in a reduction of activity below that of control levels.
Motor performance of rats of different ages was determined in a cross sectional study. The design includes a test battery of seven motor tasks of graduated complexity. The results show a hierarchical order of impairments of motor functions in aging rats; that is, the more complex the task requirement, the earlier and more pronounced is the susceptibility to deterioration of motor coordination. In spontaneous activity and swimming no difference could be observed between young and old rats. With increasing requirements for the tilting-plane, horizontal wire, climbing and chimney tests as well as the rotarod test, the older rats show a differentiated decrease in performance. The findings are discussed in respect to the theory that aging is a reverse process of early development.
In vivo turnover of NA in the brain is considerably high, but in vitro only a low activity of the enzyme DBH is detectable. It is supposed that this effect is brought about by endogenous enzyme inhibitors. It was demonstrated that the addition of rat brain homogenate, as well as different subcellular fractions from rat brain, inhibit the human serum DBH. Inhibitory activity is resistant to heat and acid but does not seem to be uniformly distributed within the cell. Pretreatment of brain homogenate with pronase reduced its inhibitory activity. In conclusion, pronase sensitive peptides are partially responsible for the inhibitory potency of tissue homogenates.
Explore the source record for details and available documents.
The development of a differential tolerance to morphine was investigated with respect to the mean effective dose, the threshold dose of tolerance, the degree of tolerance after a fixed dose, and the speed of tolerance loss. The mean effective doses, the threshold doses of tolerance, and the degree of tolerance differed considerably from effect to effect, whereas in all tests tolerance loss remained the same. The mean effective doses were not correlated to threshold doses of tolerance, degree of tolerance, or to the loss of tolerance, but a strong correlation exists between threshold doses of tolerance and degree of tolerance to all effects measured. Consequences of these results upon current theories of tolerance are discussed.
Explore the source record for details and available documents.
This study was carried out to determine whether the activity of regulatory enzymes for biogenic amines are state variables or trait variables for bipolar depression. The activity of MAO, COMT, and DBH in platelets, RBC and serum, respectively, was measured repeatedly in patients with bipolar depression and in matched control subjects. An increase in MAO activity was observed in patients compared to controls, while MAO activity was unrelated to the patient's psychopathological state. COMT activity was higher in female patients than in female controls and was lower in male patients than in male controls, but it failed to be related to the psychopathological state of patients. Relevant differences in serum DBH activity failed to occur either between patients and controls, or in patients during different states of their illness. The findings suggest that the activity of MAO and COMT are trait variables for bipolar depression, while DBH activity is neither a state variable nor a trait variable. it is discussed why only longitudinal studies in contrast to conventional cross-sectional assessments allow a distinction between state and trait variables.
Explore the source record for details and available documents.