Effects of morphine upon the pituitary-adrenal system and adrenal catecholamines: a comparative study in cats and rats

The aim of the present study was to investigate the effects of acute and chronic administration of morphine upon the pituitary-adrenal activity and adrenal catecholamines in rats and cats, two animal species with very different behavioural patterns of response to the opiate. Acute administration of the drug induced in both animal species an activation of the pituitary-adrenal system. Chronic administration of morphine to cats and rats induced a depression in the pituitary-adrenal function. No significant changes in the adrenal levels of catecholamines were observed in rats treated chronically with the drug. However, in the cat, the effects of morphine on adrenomedullary function seemed to depend on the stage of morphine treatment. The behavioural patterns of response in both animal species during chronic administration of the opiate, as well as the effects of induced withdrawal with nalorphine (an antagonist of morphine), indicated that dependence on morphine had developed, not only in the rats, but also in the cats. Acute morphine administration had a sedative effect, while in the cats the opiate produced a species-specific manic response characterized by hyperexcitement and aggressive behavior.     

Adrenocortical response to acute and chronic ethanol administration in rats

Acute ethanol administration (2 g/kg IP) induced a significant rise in serum corticosterone levels which seemed to be related to blood ethanol concentration. Chronic ethanol administration, in the form of a liquid diet for 16 or 30 days, did not alter the levels of serum corticosterone. Chronic treatment of rats with a liquid diet containing ethanol resulted in the development of tolerance.     

Role of arachidonic acid metabolism on corticotropin-releasing factor (CRF)-release induced by interleukin-1 from superfused rat hypothalami.

The present work shows that the corticotropin-releasing factor (CRF)-releasing activity of interleukin-1 (IL-1) is partially inhibited by a phospholipase A2 (mepacrine) or a cyclooxygenase (indomethacin) inhibitor, but is not affected by inhibition of the lypoxygenase pathway with norhydroguaiaretic acid. These results indicate that the metabolism of arachidonic acid plays an important role as mediator of the effects of IL-1 on CRF release. It is also shown that products of the cyclooxygenase activity such as prostaglandins can stimulate CRF secretion by a direct action on the hypothalamus. Whereas PGE2 failed to induce increases on CRF release, PGF2 alpha stimulated in a dose-dependent manner (21-340 nM), the CRF release from continuous perifused hypothalami. It is suggested that PGF2 alpha could be involved as a messenger in the hypothalamic CRF secretion induced by IL-1.     

Effects of acute and prolonged administration of chlordiazepoxide upon the pituitary-adrenal activity and brain catecholamines in sound stressed and unstressed rats

We have studied the effects of chlordiazepoxide upon the pituitary-adrenal activity (evaluated by the levels of serum corticosterone), and brain catecholamines in rats exposed to sound stimulation of 500 cycles per second at 110 decibels for 15 min. The sound stimulus itself induced a 3-fold rise in the serum corticosterone level. Acute administration of chlordiazepoxide to rats not subjected to sound stimulation induced significant increases in serum corticosterone levels; this effect was dose-dependent in the dose range of 5 to 25 mg/kg. An inhibition of the stress response was observed in rats injected acutely with the drug in doses ranging from 5 to 15 mg/kg and subjected to sound stimulation. Development of tolerance to the acute effects of the drug on the pituitary-adrenal activity was observed. Brain dopamine and noradrenaline levels showed a significant decrease after acute administration of some of the drug doses, but a dose-related effect was never observed. Prolonged treatment with chlordiazepoxide does not significantly affect the levels of either dopamine or noradrenaline at any duration of treatment.The results point to the possibility that the sites in the central nervous system mediating the depressant action of chlordiazepoxide and those mediating the anxiolytic action influence the pituitary-adrenal activity in an opposite fashion: the depressant in a stimulatory way and the anxiolytic in an inhibitory way. However, the mechanisms of tolerance development to the stimulatory or inhibitory action of chlordiazepoxide on the pituitary-adrenal activity seem to be alike.     

Naloxone decreases ethanol consumption within a free choice paradigm in rats

The effect of subcutaneous naloxone administration on the consumption of a weak ethanol solution in rats on the three consecutive days (testing days) was investigated using a behavioral paradigm which includes a first forced ethanol exposure (conditioning day) followed by a two-bottle ethanol/water choice procedure. Besides reducing fluid intake, naloxone treatment prior to forced ethanol exposure interferes with the acquisition of ethanol preference. Post-conditioning naloxone administration fails to affect ethanol preference. Administration of naloxone prior to the first testing session induces a reduction on total fluid intake, at the day of treatment; a decrease on ethanol preference throughout the three consecutive testing days is also observed with the higher dose of the antagonist (5 mg/kg). An involvement of endogenous opioids in ethanol consumption is suggested through the modulation of alcohol reinforcement or the affective quality of the gustatory cue.     

Adrenomedullary responses to acute and chronic ethanol administration to rats

The variations in levels of adrenal dopamine (DA), noradrenaline (NA) and adrenaline (A) after acute and chronic ethanol administration have been studied in rats. A relatively moderate dose of ethanol (2 g/kg) induced significant increases in DA levels, while NA and A concentrations did not change, or decreased depending on the interval of time elapsed after ethanol injection. These findings, together with those obtained in rats pretreated with alpha-methyl-p-tyrosine methyl ester (AMT), indicate an increased turnover of adrenal catecholamines (CA) after acute ethanol treatment. Chronic ethanol intake leads to significant increases in DA levels in the adrenal glands of rats subjected to ethanol feeding for 12 and 16 days; no changes were observed in NA or A concentrations in these groups of animals. After 30 days of ethanol ingestion, the levels of the three CA are within the control range, a fact that could suggest some adaptation of the sympatho-adrenal system to ethanol. After 16 days of treatment, tolerance to acute effects of ethanol on adrenomedullary system was not clear.     

Behavioral, neuroendocrine, and immunological outcomes of escapable or inescapable shocks.

The present study was designed to evaluate the effects of repeated exposure to escapable or inescapable shocks on subsequent behavior in an activity cage, and on the reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the immune system. We also studied the possible influence of behavioral factors on the behavioral and physiological impact of stress. Although exposure to different stressful situations pointed out marked differential effects in subsequent behavior, it failed to elicit differences in the neuroendocrine and immunological parameters studied. However, interesting results were found in analyzing the influence of behavioral factors. The degree of control exerted over the shock was inversely related to ACTH and corticosterone levels. In addition, individual differences in the exploratory activity to novelty were correlated with poststress lymphoproliferation and antibody formation. These data indicate that the behavioral and physiological outcomes of stress depend on the interrelations between environmental and individual factors (including both preexisting individual differences and the coping responses during stress).     

CB2 cannabinoid receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies

Amongst the various demyelinating diseases that affect the central nervous system, those induced by an inflammatory response stand out because of their epidemiological relevance. The best known inflammatory-induced demyelinating disease is multiple sclerosis, but the immune response is a common pathogenic mechanism in many other less common pathologies (e.g., acute disseminated encephalomyelitis and acute necrotizing haemorrhagic encephalomyelitis). In all such cases, modulation of the immune response seems to be a logical therapeutic approach. Cannabinoids are well known immunomodulatory molecules that act through CB1 and CB2 receptors. While activation of CB1 receptors has a psychotropic effect, activation of CB2 receptors alone does not. Therefore, to bypass the ethical problems that could result from the treatment of inflammation with psychotropic molecules, considerable effort is being made to study the potential therapeutic value of activating CB2 receptors. In this review we examine the current knowledge and understanding of the utility of cannabinoids as therapeutic molecules for inflammatory-mediated demyelinating pathologies. Moreover, we discuss how CB2 receptor activation is related to the modulation of immunopathogenic states.