Characteristics of pentobarbital discrimination in the gerbil: Transfer and antagonism

Experiment 1. Gerbils were trained in a T-shaped maze to discriminate the effects produced by pentobarbital (P-barb. 15 mg/kg, i.p.) and the effects of saline. The response, a left or right turn in the maze, was thus contingent upon the prevailing training condition (P-barb. or saline). The criterion of performing 8 correct first trial choices in 10 consecutive sessions was reached within 20 training sessions. Tests with descending doses of P-barb. yielded an ED₅₀ of 9 mg/kg. Tests with phenobarbital (40 mg/kg) or diazepam (2 and 4 mg/kg) solely maintained the drug response. P-barb. discrimination was reversed by megimide (ED₅₀: 8.5–9.6 mg/kg) and metrazol (ED₅₀: 24.9–27.9 mg/kg). Thus megimide was approximately 3 times more effective than metrazol. Metrazol (40 and 80 mg/kg) also counteracted the phenobarbital and diazepam response. Picrotoxin (2.5 and 5 mg/kg) was less effective whereas caffeine (100 mg/kg) and piracetam (100–1000 mg/kg) did not upset P-barb. discrimination. Experiment 2. Naive gerbils had to discriminate mixtures of P-barb. (15 mg/kg) plus either 40 or 80 mg/kg of metrazol from saline already at the start of the discriminative training. The drug combinations produced discriminable effects since most gerbils reached the acquisition criterion (8/10), although more slowly than gerbils trained with P-barb. solely. Gerbils trained without a drug stimulus (saline vs. saline) never attained the criterion during 60 consecutive sessions. In conclusion, reversal of established discrimination (Expt. 1) does not necessarily mean that the same drug combination lacks discriminable effects as demonstrated in Experiment 2.     

Supersensitivity of cortical neurones of the rat to acetylcholine and L-glutamate following chronic morphine treatment

Summary The effect of microelectrophoretically applied L-glutamate and acetylcholine on discharge activity of cortical neurones was studied in naive and in morphine-tolerant/dependent rats. The thresholds for increase in discharge activity elicited by these 2 putative neurotransmitters were 3 times lower in the tolerant/dependent rats than in the naive rats, indicating the development of supersensitivity.     

A controlled study on the antihypertensive effect of a new beta-adrenergic receptor blocking drug, metoprolol, in combination with chlorthalidone

1. A double-blind crossover evaluation of the antihypertensive effect of metoprolol v. placebo was carried out in a series of twenty-three patients with mild or moderate essential hypertension who were receiving chlorthalidone (25 mg daily) as their basic treatment. An individually titrated metoprolol dosage (75-300 mg) was used. The double-blind crossover study consisted of two 3-month periods during which the patients received either metoprolol or placebo in addition to chlorthalidone.

2 Metoprolol, as compared with placebo, produced a statistically significant reduction of blood pressure, both in supine and standing positions. Normotension was achieved during metoprolol-chlorthalidone treatment in twenty-two of the twenty-three patients, but during placebo-chlorthalidone treatment in only twelve of the twenty-three patients.

3 During the double-blind crossover study mild side-effects occurred during metoprolol-chlorthalidone treatment in fourteen patients during first month, in twelve patients during second month and seven patients during third month. During placebo-chlorthalidone treatment side effects occurred in seven, six and seven patients, respectively.

4 In conclusion, metoprolol caused a significant fall in blood pressure when given to patients already receiving chlorthalidone. Metoprolol in combination with chlorthalidone appears to be an effective and well-tolerated treatment for mild and moderate hypertension in those patients not responding to chlorthalidone alone.

     

Striatal dopamine transporter binding in neuroleptic-naive patients with schizophrenia studied with positron emission tomography

OBJECTIVE: Recent in vivo imaging studies indicate a dysregulated presynaptic function of the striatal dopaminergic system in patients with schizophrenia. To further explore the basis of this phenomenon, the authors studied brain dopamine transporter binding in vivo in patients with first-episode, never-medicated schizophrenia. METHOD: Nine patients with schizophrenia and nine healthy matched comparison subjects were recruited. Striatal dopamine transporter binding was measured with positron emission tomography and a specific dopamine transporter ligand, [(18)F]CFT, a radiolabeled form of 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane. RESULTS: Average caudate and putamen dopamine transporter binding potentials were almost identical in the patients and comparison subjects, but the patients lacked the right-left asymmetry of the caudate dopamine transporter binding seen in the comparison group. CONCLUSIONS: Average striatal dopamine transporter density is unaltered in neuroleptic-naive patients with schizophrenia. However, patients lack asymmetry in caudate dopamine transporter binding, which conforms with disrupted brain lateralization in this disorder.     

Effects of antipsychotic drugs on cytokine networks

It has been known since the 1950s that phenothiazines have immunomodulatory effects. This review summarizes recent evidence suggesting that antipsychotic drugs, in particular chlorpromazine and the atypical compound clozapine, influence the production of cytokines. Cytokines, organized in networks of related peptides with pleiotropic functions, are pivotal humoral mediators of infection and inflammation, and they play an important role in hematopoiesis and autoimmunity. Therefore, the effects of antipsychotic drugs on cytokine networks are important for the understanding of immune-mediated side effects of these drugs, e.g. agranulocytosis. In addition, modulation of cytokine production by antipsychotic agents suggests that these drugs might be useful for the treatment of diseases which primarily involve the immune system. Moreover, because cytokines are known to have numerous effects on the CNS, they may mediate effects of antipsychotic drugs on brain functions. Finally, the influence of antipsychotic drugs on cytokine networks is an important confounding factor in studies investigating disease-related immunopathology in psychiatric disorders. This review provides a synopsis of the data published on these topics and outlines future research perspectives.     

Neue Untersuchungen zur Typus-melancholicus-Struktur bei Migränikern

In an earlier published study [16, 17, 18], it was demonstrated that migraine sufferers have personality traits significantly more strongly associated with the typus melancholicus than healthy individuals and patients with other mental and physical illnesses. They display a fixation on tidiness which manifests itself in an excessive striving for quality and quantity in performance-oriented situations. The main features of their social relationships are excessive helpfulness combined with an exaggerated tendency towards guilt avoidance and symbiotic attachment to their own families. They do not differ from unipolar depressives in these respects. The major aim of the new study is to examine whether the concept of the typus melancholicus in relation to migraine sufferers as proposed in the first study is adaptable to explaining the personality characteristics of migraine sufferers ("typus migraenicus"). Age-matched samples of 42 female migraine sufferers, 40 female patients with unipolar depression, and 41 female control subjects took part in the new study. The test instruments used were von Zerssen's Munich Personality Test (MPT) and a questionnaire specially designed by the first author for assessing the typus migraenicus (German "Fragebogen zur Erfassung des Typus migraenicus," or FETM). The results obtained using univariate and multivariate analyses demonstrate a confirmation of the typus migraenicus concept, although to a less pronounced degree than the previous study. This can be seen as supporting evidence that, independently of the study sample and the investigators, migraine sufferers display with higher random frequency a personality profile very similar to the premorbid personality structure in unipolar depressives.     

Risk factor modification through nonpharmacological interventions in patients with coronary heart disease

Coronary heart disease (CHD) is still the main cause of death in developed countries. Because of improved treatment, many patients survive the acute phase of a myocardial infarction, which makes secondary prevention of CHD of major importance. Most risk factors responsible for the development and progression of CHD are associated with behavior. Therefore, interventions aimed at behavior change may contribute to risk factor modification and secondary prevention of CHD. The effects of separate risk factor modification efforts by means of randomized, controlled clinical trials of nonpharmacological interventions in patients suffering from CHD are reviewed. Interventions aimed at healthy lifestyles may stimulate smoking cessation rates, reduce elevated serum total and low-density lipoprotein (LDL)-cholesterol concentrations, and favorably modify type A behavior in CHD patients. Moreover, reduction of coronary atherosclerosis has been reported after intensive lifestyle and exercise interventions, whereas exercise and type A interventions may also lead to reduced CHD morbidity and mortality. As for hypertension and obesity, studies aimed at secondary prevention are lacking.     

Acute effects of interferon beta-1a on plasma cytokine levels in patients with MS

The acute effects of a i.m. injection of interferon beta-1a on the secretion of the cytokines interleukin-6, tumor necrosis factor-alpha, soluble tumor necrosis factor receptor I, and interleukin-1 receptor antagonist and its relation to peripheral concentrations of adrenocorticotropic hormone (ACTH) and cortisol in patients with MS were investigated, as well as the influence of cotreatment with indomethacin on these parameters. After interferon beta injection we found an acute rise in plasma cytokine levels and an increase in plasma hormone concentrations, both of which were modulated by indomethacin comedication.