Male Wistar rats were treated with imipramine /IMI/ /2 or 10 mg/kg, p.o./ or amitriptyline /AMI/ 10 mg/kg, p.o./ by drinking water. Each drug was given once or over periods of 1, 3, 4, 6 and 9 months. Leu-enkephalin /LENK/ content was measured by radioimmunoassay in the striatum, hypothalamus and brain perfusates after different periods of the treatment with antidepressants. A single 10 mg/kg dose of IMI increased the level of LENK in the striatum and decreased it in the hypothalamus. Six months after IMI treatment the level of LENK in the striatum was decreased after a 2 mg/kg dose and increased after 10 mg/kg; in the hypothalamus a dose-dependent increase of LENK content was observed. In brain perfusates the level of LENK was decreased 3 months after IMI treatment, but highly increased after a 9-month administration. This indicates that during prolonged treatment with imipramine the central enkephalinergic activity is dynamically changed and can affect the psychopharmacological effects of IMI. After the prolonged treatment with AMI a decrease of LENK level in the striatum was observed only after 4 months of the drug administration, and no changes were seen in the hypothalamus. It is suggested that both antidepressants studied have different action on the central enkephalinergic system.

Administration, Oral↗

PubMedDate not supplied

Conditioned fear-induced changes in neuropeptide Y-like immunoreactivity in rats: the effect of diazepam and buspirone.

The study aimed to investigate the influence of conditioned fear, produced in the passive avoidance test, on neuropeptide Y-like immunoreactivity (NPY-LI) and the effect of anxiolytics on NPY-LI in frightened rats. Rats avoided the dark chamber, where they were previously subjected to electric footshock, and they exhibited increased numbers of defecations and gastric ulcers. Moreover, they showed increased NPY-LI in the amygdala, nucleus accumbens and hypothalamus, and decreased NPY-LI in the frontal cortex. Diazepam (1 or 3 mg/kg) and buspirone (1.5 or 5 mg/kg) dose-dependently inhibited passive avoidance and decreased the numbers of defecations, and they also decreased the number of gastric ulcers. Diazepam reversed while buspirone only attenuated the fear-induced changes in NPY-LI in all regions studied. In the amygdala, the effect of diazepam was dose-dependent. The effect of diazepam on both behaviour and NPY-LI was antagonized by flumazenil (15 mg/kg). Apart from supporting the role of the NPY system in fear and anxiety, the results of this study suggest that NPY is involved in the anxiolytic effects of diazepam and buspirone and that the effect of diazepam is mediated by benzodiazepine receptors.

Amygdala↗

PubMedDate not supplied

Augmenting effect of methionine-enkephalin on interleukin-6 production by cytokine-stimulated murine macrophages.

The effects of methionine-enkephalin on the production of interleukin-6 by activated peritoneal murine macrophages were studied. Macrophage were activated with interleukin-1beta or interferon-gamma in the presence or absence of graded concentrations of methionine-enkephalin. Methionine-enkephalin combined with interleukin-1beta or interferon-gamma caused an increase in IL-6 release from cultured macrophages. The opioid receptor antagonist naloxone did not change the stimulatory effect of methionine-enkephalin on IL-6 production by stimulated macrophages. Methionine-enkephalin added to the culture medium of resting macrophages increased IL-6 release from macrophages which were later induced with interleukin-1beta or interferon-gamma. The results of this study suggest that methionine-enkephalin can modulate the proinflammatory cytokine response by controlling, via non-opioid receptor mechanism, the production of IL-6.

Animals↗

PubMedDate not supplied

Effect of substituted benzamides on feeding and hypothalamic neuropeptide Y-like immunoreactivity (NPY-LI) in rats.

The study was conducted: (i) to evaluate the effects of three substituted benzamides on feeding behaviour in rats with free access to food and in those with access to food limited either to the light or to the dark phase of the diurnal cycle; and (ii) to determine whether the hypothalamic neuropeptide Y (NPY) system is involved in the action of these drugs on feeding. In free-feeding rats, a single dose of eticlopride (1 mg/kg, i.p.) or raclopride (1 mg/kg, i.p.) decreased 24-h food intake, whereas remoxipride (3 mg/kg, i.p.) produced no effect. Single doses of eticlopride and raclopride but not of remoxipride decreased hypothalamic neuropeptide Y-like immunoreactivity (NPY-LI). Eticlopride administered once daily for 14 days decreased both food intake and hypothalamic NPY-LI. When given for 14 days, raclopride and remoxipride decreased food intake in rats with access to food in the dark (19.00-07.00) but not in thelight (07.00-19.00) phase of the diurnal cycle; both these compounds decreased hypothalamic NPY-LI only in the former group of rats. The results suggest that the effects of substituted benzamides on feeding behaviour depend on the drug and the time of administration and that these effects are related to the altered function of the hypothalamic NPY system.

Animals↗

PubMedDate not supplied

Effect of enflurane on selected neuropeptides and marker enzymes in rabbit brain.

The aim of this study was to evaluate the effect of 5-, 15-, and 60-min enflurane anesthesia on the levels of Met-enkephalin, Leu-enkephalin and neuropeptide Y in discrete areas of the rabbit brain. We also evaluated the effect of enflurane anesthesia on energetic, transport and catabolic processes by measuring the activities of succinate dehydrogenase, magnesium-dependent adenosine triphosphatase and acid phosphatase in the rabbit striatum and hypothalamus. Induction of anesthesia (5 min) decreased Met-enkephalin levels in the hypothalamus and striatum, and increased them in the hippocampus and mesencephalon. Induction of anesthesia increased Leu-enkephalin levels in all brain areas studied, except for the striatum, and increased neuropeptide Y content in the hippocampus. 15- and 60-min enflurane anesthesia increased Met-enkephalin content in the hypothalamus and hippocampus. After 15- and 60-min anesthesia, and after cessation of anesthesia, Leu-enkephalin levels were increased in the hypothalamus and mesencephalon, and were decreased in the striatum and hippocampus. In the striatum, neuropeptide Y content was significantly decreased during anesthesia and after cessation of anesthesia. Histochemical analysis revealed that enflurane enhanced ATP production, catabolic processes, and the rates of exchange and transport of energetic substrates in the striatum and hypothalamus. In conclusion, enflurane affects the levels of Met, Leu-enkephalins and NPY in a manner depending on the duration of anesthesia and the brain structure. Compared with isoflurane , which was studied in our previous study enflurane produces stronger alterations in the activities of enzymatic marker in the rabbit brain. This suggests that enflurane may be less safe than isoflurane.

Acid Phosphatase↗

PubMedDate not supplied

New vistas in immunopsychopharmacology.

The fifties of this century were a time of expansion of psychophysiology, psychopharmacology as well as immunology. But the immune system was considered by several years as completely autonomous, indetifying foreign elements to the host, and clearing them from the body. Selye was the first who put forward the hypothesis that the thymus takes part in stress phenomena and the pituitary-adrenal-endocrine system mediates the relations between stress and immune system. Then many reports on the immunological consequences of behavior were published. Herbert Novera Spector coined the term neuroimmunomodulation (NIM), and used it in the paper published in 1983. First International Workshop on NIM was held in 1985. Advances in research of the past decade brought psychoimmunopharmacology out of the folklore into the science. The perspectives of the development of understanding further details of NIM depend upon application of antisense nucleotides in further experiments, estimation of cytokine level in cerebro-spinal fluid, observations of central effects in patients treated by cytokines, measurements of several immunological, behavioral biochemical and neuroendocrine variables.

Allergy and Immunology↗

PubMedDate not supplied

Application of calcium channel blockers in the treatment of cardiovascular diseases.

In this review the calcium channel blockers (CCB) were divided into three generations. The advantages and shortcomings of these drugs were described. The application of CCB in the treatment of hypertensive disease, ischaemic heart disease, congestive heart failure and heart arrhythmias was discussed. Actually, the optimal drugs from this group are representatives of the third generation: amlodipine and lacidipine. It seems that search for new CCB should be directed to find the substances similar to or better than the chemical entities of this third generation. The calcium sensitizing agents as a new positive inotropic drugs are signalled. The possibility that in the future the new CCB could have an application as psychotropic drugs is mentioned.

Antihypertensive Agents↗