Neuroendocrine and Behavioral Effects of Flunarizine in Young and Old Rats

Cephalalgia ◽  
1985 ◽  
Vol 5 (2_suppl) ◽  
pp. 125-129 ◽  
Author(s):  
Filippo Drago ◽  
Giuseppe Continella ◽  
Orazio Mangano ◽  
Pier Luigi Canonico ◽  
Renato Bernardini ◽  
...  
Keyword(s):  
Active Avoidance ◽  
Chronic Treatment ◽  
Conditioned Avoidance ◽  
Behavioral Effects ◽  
Acute Administration ◽  
Plasma Prolactin ◽  
Acquisition Session ◽  
Old Rats ◽  
Plasma Prl ◽  
Active Avoidance Behavior

Neuroendocrine and behavioral effects following an acute or chronic treatment with the calcium antagonist, flunarizine, have been studied in young and old rats. Both in young and old rats, acute administration of flunarizine (2 mg/kg) failed to modify plasma prolactin (PRL) levels, as measured at 8.00 a.m., 4.00 p.m. and 12.00 p.m. A chronic treatment with flunarizine (0.5 mg/kg/day, for 20 days) in young rats was followed by a relevant, albeit statistically not significant, increase in plasma PRL levels, as measured at 8.00 a.m. and 4.00 p.m., and by a significant decrease at 12.00 p.m. A shift of nocturnal peak of plasma PRL levels from 12.00 p.m. to 4.00 a.m. was observed in these animals. A chronic treatment with flunarizine in old rats was followed by a significant increase in plasma PRL levels, as measured at 12.00 p.m. The acquisition of active avoidance behavior was studied in a shuttle-box test. Acute administration of flunarizine failed to change the performance of young and old rats in acquiring the behavioral response, as measured by the total number of conditioned avoidance responses (CARs) and the percentage of learners. When flunarizine was administered chronically, a decrease in CARs and learners was observed both in young and old rats. This was accompanied by a significant increase in the percentage of animals that froze during the acquisition session. No significant effect was found in young and old rats tested in a “despair” test after a chronic treatment with flunarizine.

LONG-TERM TREATMENT WITH 2—Br—α—ERGOCRYPTINE IN ACROMEGALY

1977 ◽  
Vol 85 (2) ◽  
pp. 235-248 ◽  
Author(s):  
L. Belforte ◽  
F. Camanni ◽  
P. G. Chiodini ◽  
A. Liuzzi ◽  
F. Massara ◽  
...  
Keyword(s):  
Chronic Treatment ◽  
Term Treatment ◽  
Base Line ◽  
Acute Administration ◽  
Plasma Prolactin ◽  
Long Term Treatment ◽  
Pre Treatment ◽  
A Minor ◽  
Plasma Phosphorus

ABSTRACT Thirty acromegalic subjects underwent chronic CB154 therapy (10–20 mg daily) for periods ranging from 3 months up to 2 years. In 18 out of 21 patients, who exhibited consistent HGH reduction following acute administration of the drug, there was also during chronic treatment, a suppression of the plasma HGH levels exceeding 50 % of base line values, e.g. from mean daily values between 14–197 ng/ml (mean ± sem = 57.8 ± 12.4 ng/ml pre-treatment) to 2–19 ng/ml (mean 8.3 ± 1.2 ng/ml post-treatment). In 12 of the subjects who responsed to chronic CB154 treatment, the mean daily values of HGH were below 10 ng/ml. The suppression of plasma HGH was maintained unaltered throughout the whole course of therapy. In the 9 subjects, in whom no consistent HGH decrease was evidenced with acute CB154 administration, there was accordingly a minor or no suppression of HGH values during the chronic treatment. In 13 subjects, irrespective of the degree of their GH responses, the plasma prolactin levels were constantly inhibited by CB154; instead the drug failed to modify significantly the TRH or insulin-induced GH release. These changes in the hormonal parameters were paralleled by marked clinical amelioration and improvement of some of the metabolic alterations frequently encountered in acromegaly, e.g. reduced carbohydrate tolerance, increased insulin resistance, diminished fall of plasma phosphorus after insulin, decreased urinary excretion of phosphate, hyper hydroxyprolinuria and hyper-calciuria. Collectively, these data demonstrate that CB154 thrapy is effective in reducing HGH hyper-secretion in many acromegalic patients during long-term treatment.

Age-related differences in the secretion of calcitonin in female rats

1998 ◽  
Vol 275 (5) ◽  
pp. E735-E739 ◽  
Author(s):  
Chien-Chen Lu ◽  
Shiow-Chwen Tsai ◽  
Shyi-Wu Wang ◽  
William J. S. Huang ◽  
Paulus S. Wang
Keyword(s):  
Female Rats ◽  
Ovariectomized Rats ◽  
Physiological Status ◽  
Plasma Prolactin ◽  
Middle Aged ◽  
Thyroid Glands ◽  
Old Rats ◽  
Plasma Prl ◽  
Rat Thyroid

The mechanism that causes hypercalcitonemia in female rats and is associated with aging was investigated. Young (3 mo), adult (8 mo), middle-aged (12 mo), and old (21 mo) rats were infused with CaCl2 and were bled from a jugular catheter after a CaCl2 challenge. To mimic some of the hormonal changes caused by aging, the anterior pituitary (AP)-grafted ovariectomized rats with hyperprolactinemic syndrome were used to mimic the physiological status of aging. The rat thyroid gland was incubated with or without ovine prolactin (oPRL; 40 or 80 ng/ml) at 37°C for 30 min. Old rats possessed the lowest levels of plasma estradiol and progesterone yet had the highest levels of plasma prolactin and calcitonin (CT) compared with young, adult, and middle-aged rats. The basal release of thyroid CT in vitro in thyroid glands gradually increased with age. Compared with cortex (CX)-grafted rats, the AP-grafted rats possessed higher levels of plasma PRL, basal and CaCl2-induced levels of plasma CT, and the release of thyroid CT in thyroid glands. After stimulation with oPRL, the in vitro release of thyroid CT increased in both CX- and AP-grafted rats. These results suggest that the hypersecretion of CT in old rats is due at least in part to hyperprolactinemia.

General Pharmacology of Clozapine

1992 ◽  
Vol 160 (S17) ◽  
pp. 5-11 ◽  
Author(s):  
D. M. Coward
Keyword(s):  
Locomotor Activity ◽  
Chronic Treatment ◽  
Conditioned Avoidance ◽  
Repeated Treatment ◽  
Receptor Subtypes ◽  
Plasma Prolactin ◽  
Inhibiting Activity ◽  
Extrapyramidal Side Effects ◽  
Binding Studies ◽  
General Pharmacology

Clozapine shows neuroleptic-like inhibition of locomotor activity and conditioned avoidance responding in rodents, although tolerance develops on repeated treatment. EEG-based studies show strong arousal-inhibiting activity of clozapine as well as neuroleptic-like effects on both caudate spindle duration and rat sleep-waking patterns. Effects such as apomorphine blockade, catalepsy and strong increases of plasma prolactin levels are not seen, however, and chronic treatment does not lead to dopamine D2 receptor supersensitivity. Binding studies show clozapine's highest affinities to be for dopamine D4, 5-HT1c, 5-HT2, α1, muscarinic and histamine H1 receptors, but moderate affinity is also seen for many other receptor subtypes. Microdialysis studies indicate a preferential interaction with striatal D1 receptors, whereas autoradiographical studies indicate upregulation of D1 and downregulation of 5-HT2 receptors after chronic clozapine. Clarification of the mechanisms underlying clozapine's special attributes is often hampered by a failure to examine compounds which show a close chemical relationship to clozapine, but which produce extrapyramidal side-effects in man, such as clothiapine, loxapine and amoxapine.

EFFECT OF PIRIBEDIL ON PLASMA PROLACTIN LEVELS IN WOMEN WITH PUERPERAL OR PATHOLOGICAL HYPERPROLACTINAEMIA

1977 ◽  
Vol 86 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Eugenio E. Müller ◽  
Andrea R. Genazzani ◽  
Serena Murru ◽  
Piero Fioretti
Keyword(s):  
Dopamine Receptor ◽  
Pituitary Tumour ◽  
Acute Administration ◽  
Plasma Prolactin ◽  
Clear Cut ◽  
Radiological Evidence ◽  
Receptor Sites ◽  
Plasma Prl

ABSTRACT In women with physiological puerperal hyperprolactinaemia, acute administration of Piribedil (100 mg po), a drug which stimulates dopamine receptor sites, was as effective as that of 2-Br-α-ergocryptine (CB 154, 5 mg po) in suppressing the elevated baseline plasma prolactin (PRL) levels. In two hyperprolactinaemic women with radiological evidence of an intrasellar pituitary tumour, Piribedil (100 mg po), in contrast to CB 154 (5 mg po), failed to modify plasma PRL levels, whereas in 3 other hyperprolactinaemic women with no radiological evidence of pituitary tumour, its effect was not clear-cut, even though it could not be differentiated from that of CB 154. These results indicate that Piribedil is an effective suppressor of plasma PRL levels in the human and suggest that its action is more evident in puerperal than in pathological hyperprolactinaemia.

Some Aspects of the Psychopharmacological Activity of Maprotiline (Ludiomil®): Effects of Single and Repeated Treatments

1978 ◽  
Vol 6 (6) ◽  
pp. 421-429 ◽  
Author(s):  
A Delini-Stula ◽  
E Radeke ◽  
A Vassout
Keyword(s):  
Nervous System ◽  
Chronic Treatment ◽  
Conditioned Fear ◽  
Conditioned Avoidance ◽  
Repeated Treatment ◽  
Antidepressant Effects ◽  
The Central Nervous System ◽  
Pre Treatment ◽  
High Doses ◽  
Psychopharmacological Activity

Three different aspects of the psychopharmacological activity of the antidepressant maprotiline were investigated: its influence on serotoninergic functions the effects produced by chronic treatment its central nervous depressant and anxiolytic properties. Study of the effects of maprotiline on 5-HTP-induced head-twitch in mice pre-treated with pargyline or on hyperpyrexia in rats provided no evidence that the drug interferes with serotonin-mediated functions in the central nervous system even after quite high doses. These findings corroborate the results of extensive neurobiochemical investigations, which failed to demonstrate any influence of maprotiline on the metabolism of serotonin. Chronic studies showed that classical effects of maprotiline such as antagonism against reserpine-induced ptosis or tetrabenazine-induced catalepsy do not change in their intensity after daily administration of the drugs in a dose of 30 mg/kg p.o.for 11 days. A new component of the action of the compound, not detectable after one single dose, seems to appear, however, after repeated treatment (8 days). This effect is manifested in the restoration of conditioned avoidance behaviour after its suppression by pre-treatment with reserpine. The same effect is produced by imipramine. It is suggested that this restorative effect may be due to an additional activation of the dopaminergic nervous system and may have a bearing on the appearance of clinical antidepressant effects. Maprotiline was found to potentiate central nervous depressant effects of drugs like chlorpromazine, phenobarbitone and propranolol. This affords further confirmation that, in addition to its antidepressant qualities, it possesses sedative actions. An anxiolytic component was also demonstrated in rats in which maprotiline suppressed the conditioned, fear-induced rise in body-temperature.

AP-1 TRANSCRIPTION FACTOR IN ACQUISITION OF TWO-ACTIVE AVOIDANCE BEHAVIOR

2002 ◽  
Author(s):  
J. JAWORSKI ◽  
A. SAVONENKO ◽  
K. LUKASIUK ◽  
T. WERKA ◽  
M. RYDZ ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Avoidance Behavior ◽  
Active Avoidance ◽  
Active Avoidance Behavior
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