Yukiko Tokunaga

α2-Adrenoceptors modulating diarrhoea in morphine-dependent rats

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Anticerebral antibodies in functional psychoses

Anticerebral antibodies to rabbit brain were investigated by the indirect immunofluorescence method in the sera of 44 schizophrenics and 52 depressives diagnosed according to DSM-III-R, and of 54 healthy volunteers. Four types of staining pattern were observed: type A (nerve cells), type B (blood vessels), type C (nuclei), and type D (glial cells); 34.1% of schizophrenics (27.3% after the absorption with rabbit liver acetone powder) showed type A, as compared with 3.8% (1.9% after the absorption) of depressives and with none of the controls.

Effect of Narcotic Analgesics and Naloxone on Proestrous Surges of LH, FSH and Prolactin in Rats

Morphine (50 mg/kg), given at 12:00 h and 14:00 h to proestrous rats, completely inhibited the proestrous surges of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (Prl). However, when it was given at 16:00 h, the inhibitory effect of morphine (Mor) was decreased. Pethidine and nalorphine inhibited the proestrous surges, while pentazocine showed a weaker inhibitory effect. Naloxone (Nx), given simultaneously or 2 h after morphine (Mor), at 1/20 the dose of Mor, inhibited the blockade of the proestrous gonadotropin release exerted by Mor, while the onset of the surges was delayed when it was given 3 h after Mor.

Acute physical dependence induced by continuous intravenous infusion of morphine or meperidine in the rat.

An intravenous infusion method is described for rapidly producing physical dependence in rats. Rats were infused with morphine or meperidine for 24 or 48 h at constant rates and the development of physical dependence was assessed by body weight loss after naloxone challenge. Naloxone challenge induced body weight losses that were dependent upon magnitude, rate and duration of infusion. The steady-state concentrations of morphine (4 mg/kg/h) in serum and meperidine (6 mg/kg/h) in plasma were 4 and 2.5 μg/ml, respectively. Morphine concentration in the brain in the steady-state (4 mg/kg/h) was 0.7 μg/g and in the serum was proportional to the infusion rate. Maximum body weight loss was significantly correlated with total amount of infused morphine, but not with the steady-state concentration of the drug in the serum. These results suggest that total doses of infused morphine, not steady-state concentrations, are critical in producing body weight loss.

Effect of narcotic analgesics on plasma cyclic AMP levels in male mice

Abstract Systemic administration of morphine, as well as pethidine and pentazocine, increased plasma cyclic AMP levels in male mice. Intracerebroventricular administration of morphine and β-endorphin also increased plasma cyclic AMP levels. The effect of morphine and β-endorphin was antagonized by naloxone indicating the involvement of opiate receptors in the central nervous system for the effect of morphine on cyclic AMP levels. Tolerance was shown to develop to the action of morphine in increasing the plasma cyclic AMP. The morphine-induced increase in plasma cyclic AMP was abolished by treatment with propranolol or pentolinium or by adrenalectomy but not by treatment with atropine, phentolamine, 6-hydroxydopamine or α-methyltyrosine. These findings suggest that morphine increases plasma cyclic AMP levels mainly by releasing catecholamines, from the adrenal medulla, and these activate adenylate cyclase via the stimulation of β-adrenoceptors.

Inhibition by cholinergic agonists of the prolactin release induced by morphine

SummaryThe cholinergic agonists, pilocarpine, physostigmine and nicotine, inhibited the prolactin release induced by morphine in male rats in vivo. Pilocarpine also inhibited the release of prolactin induced by β-endorphin or metoclopramide without affecting the basal and haloperidol-stimulated serum prolactin levels. The inhibitory effect of pilocarpine on the morphine-stimulated release of prolactin was antagonized by concurrent administration of atropine but not by atropine methylnitrate or by mecamylamine, while the inhibition by nicotine was antagonized by mecanylamine but not by atropine. The stimulation of prolactin release by morphine and its reversal by pilocarpine were observed after the administration of haloperidol or α-methyltyrosine. These results suggest that the central cholinergic system exerts an inhibitory influence on the prolactin release induced by morphine or β-endorphin and the cholinergic inhibition is not mediated via catecholaminergic neurons.

Plasma cyclic amp in the morphine-tolerant rat

Abstract Effects of morphine on plasma cyclic AMP leveis in the rat were investigated. Morphine (20 mg kg , s.c. + 4 mg kg/hr , i.v.) produced an increase in plasma cyclic AMP concentrations at 1hr and sustained elevated levels for several hours, but the levels returned to normal levels at 48 hr. the 48 hr increase in plasma cyclic AMP elicited by morphine (20 mg kg , s.c.) was far smaller than that of 1 hr; the plasma concentration of morphine was at the same level as the 1 hr. This indicated the development of tolerance to the morphine induced increase in plasma cyclic AMP. At 48 hr an epinephrine challenge increased plasma cyclic AMP to the same extent as in naive rats. Therefore, desensitization of peripheral tissues as being responsible for the increase in the plasma cyclic AMP could be ruled out. the development of tolerance by the sympatho-adrenal reflex elicited by morphine was suggested. In naioxone-precipitated abstinence, plasma cyclic AMP showed a 4-fold increase but. on spontaneous withdrawal, it showed on a slight but significant increase. It was concluded that plasma cyclic AMP is a sensitive index of tolerance to and dependence on morphine.

Effects of repeated administration of potassium canrenoate (SC-14266) on serum gonadotrophin, prolactin, testosterone and progesterone in male rats.

Chronic administration of potassium canrenoate (SC-14266), a water-soluble anti-aldosterone agent, increased serum LH levels in male rats without altering serum levels of FSH, prolactin, testosterone and progesterone. The increase in serum LH may be due to the anti-androgenic effect of potassium canrenoate.

Effect of chlorpromazine on plasma adenosine 3',5'-cyclic phosphate level.

A subcutaneous injection of chlorpromazine hydrochloride (CPZ) at a dose of 10 mg/kg caused an increase in the plasma cyclic AMP level in male mice. Propranolol (2 mg/kg) and hexamethonium (50 mg/kg) abolished the elevation of plasma cyclic AMP induced by CPZ. Phentolamine (5 mg/kg) could not inhibit the effect of CPZ. Adrenalectomy completely inhibited the elevation of plasma cyclic AMP produced by CPZ. Pretreatment with 6-hydroxydopamine (100 mg/kg, i.v., 24 hr before) failed to reduce the elevation of the plasma cyclic AMP level produced by CPZ. Intracere-broventricular administration of CPZ (5-25 microg/mouse) also increased plasma cyclic AMP levels. These findings indicate that CPZ activated the sympathetic nervous system by acting on the CNS, thereby increasing plasma cyclic AMP levels through the stimulation of beta-adrenoceptors mainly by catecholamines released from the adrenal medulla.

Increase in plasma cyclic AMP levels elicited by naloxone in morphine-dependent male mice ☆

Abstract Naloxone increased the levels of plasma cyclic AMP in morphine-dependent male mice in which a morphine pellet had been implanted for 72 hr, but not in the nondependent mice. The effect of naloxone on the cyclic AMP levels disappeared 24 hr after the removal of the morphine pellet. Pretreatment with propranolol, hexamethonium or adrenalectomy, but not with atropine or phentolamine inhibited the effect of naloxone. These results suggest that naloxone increases the level of plasma cyclic AMP by releasing catecholamines from the adrenal medulla, thereby activating the adenylate cyclase in the tissues through the stimulation of β-adrenergic receptors. A moderate increase in plasma cyclic AMP was also seen in morphine-dependent mice 1 hr after the removal of the morphine pellet. It is proposed that the increase in the levels of plasma cyclic AMP elicited by naloxone-precipitated or abrupt withdrawal is one of the withdrawal symptoms and probably can be used as a screening method for assessing the degree of physical dependence in laboratory animals.