High Doses Of Bromocriptine Research Articles

Comparative Effect of Selected Ergot-Derived Dopamine on the Kidney Function of Wistar Rats

Ergot derived dopamine are chemical derivatives used in the treatment of certain conditions and disorders. The use of these drugs, despite its numerous heath advantages can pose a threat to the health and general metabolism when administered in unprescribed doses and time. This study evaluated the comparative effect of bromocriptine and cabergoline on the functionality and integrity of the Kidney. Twenty albino rats of wistar grain, weighing between 100-180g were used for this study. They were grouped into 5 groups with each of the group containing 5 rats. Group 1 was the control group, Group 2-5 were Low dose Bromocriptine, High dose Bromocriptine, Low dose Cabergoline, and High dose Cabergoline respectively. The drugs were administered at the various doses on a 24-hour basis. After a period of 21 days, the animals were sacrificed and blood samples were collected for bioassay on the urea, creatine and serum electrolytes as indicators of kidney function using Standard laboratory procedures, the kidney was harvested for histological examination.

Comparative evaluation on the effect of selected ergot-derived dopamine on some female reproductive hormones in Wistar rats

Background: Hormonal imbalance can occur during some disease conditions, while in some other cases, an increase or decrease in the levels of the female hormones in the body might be associated with adverse effects from drugs and may also pose the risk of infertility and Ovarian cancers when these drugs are abused. Although the dopamine agonists have been helpful in ameliorating some disease conditions, it could also cause an adverse effect on the reproductive hormones and other organs of the body. Objective: This study comparatively evaluated the effect of Bromocriptine and Cabergoline on some female reproductive hormones. Methodology: This study was carried out using twenty-five rats grouped into five groups of five rats in each. Group one was the control group, Group 2 and 3 were low and high dose of Bromocriptine, while Group 4 and 5 were low and high dose Cabergoline. The drugs were administered twenty-four hourly and lasted for 21 days. Blood samples were collected for hormonal assay. Results: The results for the bioassay of FSH, LH, PROG, PRO and Estrogen revealed that both low and high dose of Bromocriptine and Cabergoline administered to the Wistar rats caused an increase in the concentration of FSH, LH, Progesterone, Prolactin and Estrogen. The level of Prolactin and Estrogen increased significantly at 0.05 level. However, a decrease was observed in prolactin and estrogen level when administered High dose bromocriptine and Low dose cabergoline respectively. Conclusion: This assessment therefore suggests that both Cabergoline and Bromocriptine had no adverse effects on the female reproductive hormones, however, Cabergoline may pose greater effectiveness than bromocriptine, hence adherence to prescription is necessary for effectiveness.

Malignant Catatonia Requiring High Dose Bromocriptine: Case Report

Catatonia can occur in patients diagnosed with schizophrenia and bipolar disorder and malignant catatonia is life threatening. Anti-psychotic medications should be discontinued during acute phase of catatonia. Anti-psychotic discontinuation in catatonia is a challenge in patients maintained on long-acting injectable antipsychotics because of the extended release. Case report: We present a case of malignant catatonia developed in a patient with history of schizophrenia and developmental delay. Symptoms lasted several weeks as he was recently administered long acting injectable antipsychotic medication, requiring high dose Bromocriptine treatment. Patient required several days of bromocriptine treatment. Because of the shorter half-life, frequent and higher dosing of bromocriptine led to resolution of malignant catatonia. Malignant catatonia is a medical emergency and prompt treatment including high dose bromocriptine could lead to resolution of catatonia.

Dose-Dependent Changes in Auditory Sensory Gating in the Prefrontal Cortex of the Cynomolgus Monkey.

BackgroundSensory gating, often described as the ability to filter out irrelevant information that is repeated in close temporal proximity, is essential for the selection, processing, and storage of more salient information. This study aimed to test the effect of sensory gating under anesthesia in the prefrontal cortex (PFC) of monkeys following injection of bromocriptine, haloperidol, and phencyclidine (PCP).Material/MethodsWe used an auditory evoked potential that can be elicited by sound to examine sensory gating during treatment with haloperidol, bromocriptine, and PCP in the PFC in the cynomolgus monkey. Scalp electrodes were located in the bilateral PFC and bilateral temporal, bilateral parietal, and occipital lobes. Administration of bromocriptine (0.313 mg/kg, 0.625 mg/kg, and 1.25 mg/kg), haloperidol (0.001 mg/kg, 0.01 mg/kg, and 0.05 mg/kg), and the N-methyl-D-aspartic acid receptor antagonist PCP (0.3 mg/kg) influenced sensory gating.ResultsWe demonstrated the following: (1) Administration of mid-dose bromocriptine disrupted sensory gating (N100) in the right temporal lobe, while neither low-dose nor high-dose bromocriptine impaired gating. (2) Low-dose haloperidol impaired gating in the right prefrontal cortex. Mid-dose haloperidol disrupted sensory gating in left occipital lobe. High-dose haloperidol had no obvious effect on sensory gating. (3) Gating was impaired by PCP in the left parietal lobe.ConclusionsOur studies showed that information processing was regulated by the dopaminergic system, which might play an important role in the PFC. The dopaminergic system influenced sensory gating in a dose- and region-dependent pattern, which might modulate the different stages that receive further processing due to novel information.

Differential effects of dopamine receptor subtype-specific agonists with respect to operant behavior maintained on a differential reinforcement of low-rate responding (DRL) schedule

Previous studies have shown that d-amphetamine, a dopamine (DA) indirect agonist, alters operant responding with respect to the behavior maintained on a differential reinforcement of low-rate (DRL) schedule of reinforcement. These behavioral changes have been presumed to result from drug-induced hyperdopaminergia that leads to activation of DA receptors. This study investigated the acute dose effects of DA receptor subtype-selective agonists on the performance of DRL 10-sec behavior by rats. SKF38393 (a D1 receptor agonist) and quinpirole (a D2/D3 receptor agonist) were able to dose-dependently disrupt DRL 10-sec behavior by decreasing the total responses, the non-reinforced responses, and the peak rate of response. Bromocriptine (a D2/D3 receptor agonist) produced a significantly different pattern of behavioral changes when examined during two distinct time phases (15min and 3hr after the drug injection). DRL responding was only altered at higher doses of bromocriptine in the second phase as indicated by decreasing reinforced responses and peak rate, together with an increase of burst responses. In contrast to the D1 and D2/D3 receptor agonists, PD168077 (a D4 receptor agonist) did not affect DRL 10-sec behavior. None of these tested drugs affected DRL 10-sec behavior in a manner similar to that of d-amphetamine. These findings show that there are differential effects on the performance of DRL 10-sec behavior when drugs are able to preferentially activate D1, D2/D3 and D4 receptors, supporting the assertion that there is functional heterogeneity of the DA receptor subtypes.

Understanding the neurotransmitter changes underlying cognitive dysfunction in traumatic brain injury and possible therapeutic targets: a review.

Traumatic brain injury (TBI) is the primary cause of death and disability in younger individuals [1]. To date, the mechanism behind the cognitive dysfunction following TBI remains unclear. Neurotransmitters (NT) represent a particularly important system in physiological events relevant to cognition affected by TBI [2]. Preclinical evaluations of both agonists and antagonists affecting acetylcholine (Ach) and the dopamine (DA) system have shown marked benefits for cognitive recovery. Hence, the aim of this article is to outline clinical studies that have shown potential efficacy of Ach- and DA-oriented medications in the treatment of TBI. PubMed was used to search for articles published since 1998 that reported any association between cognitive dysfunction following TBI. Before 1998, no clinical studies regarding the neurotransmitter-targeted therapies in TBI had been reported. After reviewing the abstracts, 14 articles were submitted to the final evidence review. Acetylcholinesterase (AChE) inhibitors are most beneficial for the treatment of posttraumatic cognitive impairments [3]. Principally, rivastigmine improved the cognitive function in TBI patients [4]. However, the results from randomized controlled trials have remained modest [5]. Zhang et al. [6] performed a 24-week, randomized, placebo-controlled, double-blind crossover trial to demonstrate sustained improvements in immediate auditory and visual memory, attention, working memory and information processing speed. An open-label study conducted by Tenovuo [7] also found a subjective and longer (average 24 months) improvement following donepezil (summarized in Table I). Table I Acetylcholinesterase inhibitors for cognitive rehabilitation after TBI Dopamine represents a unique role in the NT system within the central nervous system (CNS) due to its influences on a number of physiologic functions including working memory, behavioral flexibility, and decision making [8]. In 2006, the Neurotrauma Foundation (NTF) recommended three drugs with DAergic effects to be used in TBI patients to enhance cognitive recovery and rehabilitation [9]. The identified drugs were methylphenidate (MPD), amantadine hydrochloride (AMH), and bromocriptine [9]. Multiple studies have demonstrated the effectiveness of MPD used in TBI patients with cognitive dysfunction especially in information processing speed [10], attention [11, 12], alertness [13], and working memory [14] after brain trauma. However, there is no longer than six months follow-up in the clinical trials regarding MPD in patients with TBI. Amantadine hydrochloride has also been found to be effective at treating cognitive dysfunction post-TBI in both clinical trials and case reports. Kraus et al. [15] showed that AMH treatment improved prefrontal executive function in TBI patients correlated with an increase in left prefrontal cortex glucose metabolism. Patrick et al. [16] reported that AMH accelerated recovery of attention deficit in children with a lower response following brain injury. Bromocriptine is a specific D2 receptor agonist, and a past case report [17] showed improvements in motor function and executive function after administering bromocriptine in a severe TBI patient associated with Parkinson's syndrome. In contrast, McDowell et al. did not find that bromocriptine appeared to improve attentional difficulties in moderate to severe TBI patients. However, this study employed a relatively high dose of bromocriptine at 10 mg/day for a more prolonged treatment period than previously studied in TBI [18]. In addition, a 6-week placebo-controlled pilot study showed that bromocriptine in TBI patients also did not enhance attentional skills [19] (summarized in Table II). Table II Dopamine drugs for cognitive rehabilitation after TBI This brief review has sought to summarize the evidence that supports an NT-oriented hypothesis of cognitive dysfunction after TBI and provide a context for the use of Ach and DA targeted therapies during patient rehabilitation. In conclusion, it seems that applications of AChE inhibitors and DA agonists are beneficial in TBI patients with cognitive dysfunction.

A study of prevention and regression of cardiac hypertrophy with a prolactin inhibitor in a biological model of ventricular hypertrophy caused by aorto caval fistulae in rat

The possibility of decreasing or reverting left ventricular hypertrophy and, therefore, cardiac hypertrophy (CH) is an important medical issue. The aim of the present study was to evaluate these two possibilities with a 3-week daily dose of captopril, losartan, or bromocriptine in a preventive or corrective model. After aorto caval fistulae (ACF) surgery on adult male Wistar rats to induce CH, animals were assigned to the preventive protocol (drug treatment began immediately after surgery) or corrective protocol (hypertrophy was allowed to develop before drug treatment). After treatments, isoproterenol was administered to half of the animals to further induce CH. The groups included the passive control, the sham-operated animals, those with ACF surgery but without drug treatment, and the 3-week treatments with captopril, losartan, or the low or high dose of bromocriptine. Three treatments, with captopril, losartan, or the high dose of bromocriptine, significantly impeded/reverted an increase in CH-related parameters in the preventive/corrective model compared to the surgically treated group without drug treatment. The same effect was found after isoproterenol administration. The present results show an avoidance/reversion of CH with these three treatments. Better results were found with the angiotensin converting enzyme inhibitor (captopril) than with the prolactin inhibitor (bromocriptine). Treatments with captopril, losartan, and the high dose of bromocriptine were effective in preventing/reversing the manifestation of CH in the preventive/corrective rat models. Further studies are needed to identify the initial mediator, the key component, and the molecular events involved in the pathogenesis of CH.

Remarkable effects of cabergoline in a patient with huge prolactinoma resistant to high-dose bromocriptine: case report

Background Cabergoline (CAB) has been proposed as the first-line treatment in the management of prolactin (PRL)–secreting tumors (prolactinoma [PRLoma]), including those resistant to standard dopamine agonist (DAA) therapy. The authors report remarkable effects of CAB in a case of huge PRLoma that had been resistant to a long-term, high-dose treatment with bromocriptine (BRC). Case Description A 28-year-old man was originally presented with oculomotor paresis when he was 9 years old. After 2 partial resections, he was treated with a maximum 60-mg/d dose of BRC for 18 years. Nonetheless, the tumor grew up to more than 8 cm in diameter, serum PRL increased over 60 000 ng/mL, and his visual acuity deteriorated. Cabergoline normalized serum PRL level, shrank the tumor mass remarkably, and caused marked improvement of visual acuity. Conclusion Prolactin normalization and significant tumor shrinkage could be achieved with CAB even in extremely BRC-resistant PRLomas. Surgical resection should be reserved only for patients who are resistant to cabergoline or who require urgent decompression in such emergency as massive intratumoral hemorrhage.

Long-term response of pituitary carcinoma to temozolomide

Pituitary carcinoma is a rare tumor characterized by poor responsiveness to therapy, leading to early death. Reported responses to standard chemotherapy have only been anecdotal, with no single agent or combination demonstrating consistent efficacy in the treatment of patients with this disease. The authors report rare examples of a persistent response to cytotoxic chemotherapy in two patients with pituitary carcinoma. One patient was a 38-year-old man with visual field loss caused by a luteinizing hormone-secreting pituitary carcinoma that had recurred despite multiple surgeries and radiation therapy. Intradural metastases to the spine that had failed to respond to radiation therapy were pathologically confirmed. The second patient was a 26-year-old man with hyperprolactinemia from a prolactin-secreting pituitary tumor. Spine magnetic resonance images obtained to search for causes of neck pain showed a vertebral tumor, which was later confirmed through pathological analysis to be a metastatic pituitary carcinoma. His disease progressed despite radiation therapy, high-dose bromocriptine, and chemotherapy. Both patients were treated monthly with temozolomide, which was administered orally on the first 5 days of a 28-day cycle. The patient in the first case underwent all 12 treatment cycles without serious side effects, and his visual field deficits improved. The patient in the second case had undergone only 10 cycles when the drug was stopped because of his severe fatigue. Nonetheless, his pain disappeared and his serum prolactin concentration decreased. Both patients continue to have partial responses and have been employed full-time for more than 1 year after discontinuing temozolomide therapy. These two examples demonstrate that temozolomide may be effective in treating pituitary carcinomas and thus should be considered in the treatment algorithm for these difficult cases.

Complete remission of hyperprolactinemia and erythrocytosis after hysterectomy for a uterine fibroid in a woman with a previous diagnosis of prolactin-secreting pituitary microadenoma

A 44-year-old woman who had been suffering for 10 years from amenorrhea and hyperprolactinemia resistant to high doses of bromocriptine was hospitalized with erythrocytosis, normal serum erythropoietin (sEpo) levels, and hypertension. Erythrocytosis secondary to uterine myoma and a prolactin-secreting pituitary microadenoma were initially diagnosed. The hyperprolactinemia was bromocriptine resistant, despite gradual increase of the dosage to 30 mg/day. Both hyperprolactinemia and erythrocytosis unexpectedly regressed completely after the patient underwent hysterectomy for a uterine fibroid 9 months after the erythrocytosis was first disclosed. Given the well-known effects of prolactin on hematopoietic cells, we hypothesize that--in this very unusual case--the two main, apparently unrelated abnormalities (erythrocytosis with normal sEpo levels and hyperprolactinemia) may have been the clinical consequence of the functional redundancy and pleiotropy of the "pituitary" hormone prolactin, inappropriately secreted by a uterine fibroid for more than 10 years.

Effect of BCH 325 (Pro-D-Phe-Pro-Gly) on central dopaminergic functions.

Three behavioral models were used to characterize the pharmacological action of BCH 325 on central dopaminergic transmission. The effect of acute SC treatment with BCH 325 upon dopaminergic mechanisms affecting motor activity was studied on the climbing behavior of mice. It was shown that the beta-casomorphin analogue evoked a dose-dependent increase in apomorphine (APO)-induced hypoactivity that was reversed by sulpiride (SULP). In in vitro studies on slices of nucleus accumbens of mice it could be demonstrated that 10(-6) M APO caused a reduction of K(+)-stimulated [14C]dopamine (DA) release that was potentiated following simultaneous incubation with 10(-6) M BCH 325. To prove a postsynaptic influence in D1 receptor-mediated behavior pattern, the action of BCH 325 was studied on bromocriptine (BROMO)-evoked yawning behavior of rats after pretreatment with reserpine (RES) or saline. The peptide could not influence the BROMO yawning after saline administration, but it was able to normalize the number of yawns, which were reduced after RES. To investigate the effect of BCH 325 on postsynaptic D2 receptors, jerking behavior on RES-pretreated rats after a high dose of BROMO was used. Following RES pretreatment only, the number of BROMO-induced jerks was decreased by treatment of rats with 0.5 mumol/kg BCH 325. In contrast, the jerking behavior was enhanced by 0.5 mumol/kg BCH 325 in rats that were additionally treated with alpha-methyl-p-tyrosine (MPT). In biochemical studies on slices of the nucleus accumbens of mice, the in vivo pretreatment with RES caused a reduction of K(+)-stimulated [14C]DA release that was blocked by the SC administration of 0.5 mumol/kg BCH 325.(ABSTRACT TRUNCATED AT 250 WORDS)

Bromocriptine-induced dystonia in patients with aphasia and hemiparesis.

Five of seven patients with chronic nonfluent aphasia and hemiparesis due to a focal ischemic infarction developed painful hemidystonia during treatment with a high dose of bromocriptine. All seven patients had cortical damage, but four also had basal ganglia and one thalamic involvement. While lesion location did not differ between dystonic and nondystonic patients, the dystonic patients had more weakness than those without dystonia.

Malignant Prolactinoma With Extracranial Metastases

Objective Prolactin-secreting tumours of the pituitary almost never metastasize extracranially. However, we have recently seen three such patients, whose presentation, clinical course and response to treatment are reviewed in order to determine whether they possess unique clinical features, and to assess optimum therapy. Design and patients Three patients with extracranial metastases from prolactinomas have been retrospectively reviewed. Measurements Clinical courses, biochemical parameters and imaging modalities (CT, MR and radiolabelled somatostatin analogue scanning) and histopathology were assessed before and during different therapeutic regimens. Results All three patients' presentations were initially unremarkable, but later each had persistent and relentlessly increasing serum prolactin concentrations and evidence of distant spread of their tumours. The first patient presented aged 32 and was treated with repeated transsphenoidal resections of the tumour, pituitary radiotherapy, high dose bromocriptine therapy, the somatostatin analogue octreotide and chemotherapy. Nine years after the original diagnosis a liver biopsy revealed carcinoma cells positively immunostaining for prolactin. At autopsy further microscopically similar metastases were seen in both lungs and the left hilar lymph nodes. The second patient presented aged 48 and was treated with external beam pituitary radiotherapy, bromocriptine, transsphenoidal hypophysectomy and chemotherapy. Fifteen years after the original diagnosis bone biopsy revealed carcinoma cells positively immunostaining for prolactin; the patient developed interstitial nephritis and died in renal failure. The third patient presented aged 48 with hypogonadism and bitemporal hemianopia due to a macroadenoma. This was removed transfrontally and followed by external beam radiotherapy. After recurrence, further surgery and radiotherapy were undertaken, but the tumour continued to grow and the patient died suddenly of a pulmonary embolus. At autopsy, tumour was found in thoracic lymph nodes and lung capillaries. Conclusions These three patients may be added to the previous two reported cases of malignant prolactinoma with extracranial spread. Several different therapies were tried but were of limited value in controlling the progression of the disease, although chemotherapy is an important modality to be considered. No particular factor or combination of factors at presentation differentiated these patients from more typical patients whose disease is much less aggressive.

Effects of Bromocriptine Treatment on Immune Responses and 3–Methylcholanthrene-Induced Tumorigenesis in Rats

Seven-week-old male Sprague-Dawley rats were given a single injection of 1.5 mg of 3-methylcholanthrene (3MC) to induce in situ fibrosarcomas. The rats were also treated with the dopamine agonist bromocriptine (BCR) from two days prior to 14 days after 3MC treatment and again for 14 consecutive days beginning at week 5. Tumor incidence was markedly increased and latency decreased in BCR-3MC rats compared to 3MC controls. Natural killer (NK) cell cytotoxicity responses and production of interleukin 2 (IL2) was enhanced at two weeks in rats treated with only BCR. Natural killer cell activity was suppressed at two weeks in rats treated with only 3MC. This effect was reversed by BCR treatment. Rats treated with 3MC and BCR had suppressed NK cell responses and production of IL2 and interferon-gamma (IFN) at 12 weeks. In another study, rats injected with 1, 3 or 5 mg/kg BCR for 14 consecutive days had increased NK cell activity and IL2 production at all doses and increased IFN production at the two high doses. Antibody (IgG) responses to an injected antigen and delayed-type hypersensitivity reactions were not affected by BCR treatment. Animals treated with the two high doses of BCR had decreased serum prolactin (PRL) levels. Serum growth hormone (GH) concentrations were markedly increased in the group treated with 3 mg/kg BCR. These data suggest that BCR enhances 3MC-induced tumorigenesis. The mechanism of this effect is apparently not mediated by suppression of the immune system since BCR-treated rats had selectively enhanced immune function. Enhancement of immune responses by BCR has not been previously reported.

Bromocriptine induces climbing behaviour: possible D-1 or D-2 dopamine receptor involvement

The ability of bromocriptine (BRC), a dopamine D-2 receptor agonist, to induce climbing behaviour was studied in mice. BRC (2-32 mg/kg IP) evoked climbing behaviour. The maximum effect was obtained with 8 mg/kg, while higher doses of BRC (16 and 32 mg/kg) were less effective. Climbing began about 2 h after injection and was most marked 5 h after bromocriptine administration. Pretreatment of animals with the dopamine antagonist pimozide (0.5 mg/kg IP) decreased BRC-induced climbing. Sulpiride (0.25-1.25 mg/kg IP), a potent D-2 antagonist and/or SCH 23390 (0.025 and 0.05 mg/kg SC), a D-1 receptor antagonist, also decreased the response. Furthermore, the climbing behaviour induced by BRC was abolished by pretreatment with reserpine plus alpha-methyl-p-tyrosine (AMPT). Concomitant administration of apomorphine (APO) and BRC potentiated the effect of APO on climbing. Concomitant injection of BRC and SKF 38393 (SKF, D-1 agonist) reduced the effect of SKF on climbing, while administration of BRC 4 h before SKF potentiated the effect of both drugs. It is suggested that BRC induces climbing through D-1 and/or D-2 dopamine receptors.

The Behavioral Toxicity of Bromocriptine in Patients with Psychiatric Illness

Dopamine agonists may be useful in the treatment of neuroleptic-induced hyperprolactinemia and movement disorders; it is a treatment approach that has been avoided for fear of inducing or exacerbating psychotic symptoms. The risks of giving dopamine agonists to psychiatric patients have been well documented in the literature. To further evaluate the psychotogenic effects of bromocriptine, a dopamine receptor agonist, we conducted a double-blind study in which 16 psychiatrically stable patients were treated for tardive dyskinesia with neuroleptics plus high doses of bromocriptine (N = 11) or placebo (N = 5) for 10 weeks. The diagnoses included schizophrenia, schizoaffective disorder, and major depression with psychotic features. Patients were evaluated weekly with the Brief Psychiatric Rating Scale and the Clinical Global Impression Scale during the 10-week treatment phase and for 8 weeks after medication was withdrawn. There were no statistically significant differences between active and placebo groups in behavioral ratings at baseline, week 10, and week 18. These results are compared with the findings of previous studies in which bromocriptine was given to psychiatric patients. Although the literature suggests that bromocriptine can induce or exacerbate psychosis in psychiatric patients, this occurs primarily in those with a psychotic diathesis and who are not currently receiving neuroleptic medication. Other important factors include the dose of bromocriptine, duration of treatment, and the clinical state of the patient at the time bromocriptine treatment is initiated. These results suggest that bromocriptine can be safely used in patients at risk for psychotic illnesses as long as patients are clinically stable and maintained on neuroleptics.

Effects of chronic long-acting bromocriptine treatment on liveweight, voluntary food intake, coat growth and breeding season in non-pregnant red deer hinds.

Seventeen red deer hinds were housed in individual pens and from 28 February until 11 November were injected each week with vehicle (group A; n = 6) or 5 (group B; n = 6) or 12.5 mg (group C; n = 5) of a long-acting formulation of bromocriptine. Liveweight and voluntary food intake (VFI) were recorded for each hind, and blood was collected for determination of progesterone, prolactin, tri-iodothyronine (T3) and cortisol concentrations by radioimmunoassay. Treatment with the high dose of bromocriptine was associated with a significant (P less than 0.05) reduction in VFI, with the effect being greatest between March and July. There was no treatment effect on liveweight, but there was a significant (P less than 0.01) interaction between time and treatment due to the faster rate of weight gain in control animals at the beginning of the experiment. Changes in liveweight could be explained by changes in VFI rather than by changes in the efficiency of utilization of intake. Termination of the breeding season was significantly (P less than 0.01) delayed by 54 days in group C hinds. Growth of the summer coat and subsequent winter coats was delayed by 1 and 3 months respectively in group C hinds, and in groups B and C the duration that animals were in summer coat was increased by about 1 month. The seasonal increase in prolactin concentrations was seen in all groups, but levels were significantly (P less than 0.05) lower in group C hinds. Concentrations of T3 and cortisol were not affected by bromocriptine.

The mode of action of bromocriptine following pretreatment with reserpine and ?-methyl-p-tyrosine in rats

The ability of bromocriptine (BRC), a selective dopamine D-2 receptor agonist, to induce yawning responses was studied in rats pretreated with reserpine and alpha-methyl-p-tyrosine (alpha-MPT). BRC (1 20 mg/kg IP) evoked yawning responses, which were pronounced at 2.5 mg/kg and characterized by the head moving downward. Higher doses of BRC (5 20 mg/kg) dose-dependently delayed the onset and peak time of yawning. A low dose of the selective D-1 dopamine receptor agonist SK&F38393 did not induce yawning but enhanced the BRC-induced response. Pretreatment with reserpine (1 and 5 mg/kg SC), alpha-MPT (100 and 300 mg/kg IP) and reserpine (1 mg/kg) plus alpha-MPT (100 mg/kg) was able to significantly reduce BRC-induced yawning. The inhibitory effects were prevented by a low dose of SK&F38393 (0.5 mg/kg IP). In particular, combined treatment with reserpine (5 mg/kg) and BRC (10 and 20 mg/kg) elicited upright fighting and jumping behaviors which were inhibited by haloperidol (1 mg/kg IP), a non-selective D-1 and D-2 receptor antagonist, SCH23390 (0.05 mg/kg SC). a selective D-1 receptor antagonist, or sulpiride (20 mg/kg IP), a potent D-2 receptor antagonist, and were potentiated by SK&F38393 (0.5 mg/kg). SCH23390 (0.05 mg/kg) decreased BRC-induced yawning and the apomorphine (low doses)-induced potentiation of BRC yawning, and prevented the apomorphine (high doses)-induced reduction of BRC yawning. SCH23390 also inhibited apomorphine-induced stereotypy and BRC-induced potentiation of apomorphine stereotypy.(ABSTRACT TRUNCATED AT 250 WORDS)

Multifocal sites of action involved in dopaminergic-cholinergic neuronal interactions in yawning.

Bromocriptine (BRC), a dopamine D-2 receptor agonist, physostigmine, an anticholinesterase agent and pilocarpine, a muscarinic cholinergic receptor agonist, produced yawning in rats, with the most effective doses being 2.5 mg/kg, 0.2 mg/kg and 4 mg/kg, respectively. BRC-induced yawning was inhibited by high doses of SK&F38393 (5 and 10 mg/kg), a selective D-1 receptor agonist. BRC or SK&F38393 alone did not induced stereotyped behaviors. However, when BRC was administered after SK&F38393 (5.0 and 10 mg/kg), stereotyped behaviors occurred; i.e., mainly sniffing at 2.5 and 5.0 mg/kg BRC, and mainly licking and biting 10 and 20 mg/kg BRC. A high dose of apomorphine (4 mg/kg IP) completely inhibited physostigmine-induced yawning (physostigmine yawning) but did not affect pilocarpine-induced yawning (pilocarpine yawning). BRC (2.5 20 mg/kg) increased physostigmine yawning in an additive fashion. Pilocarpine yawning was completely blocked by either low or high doses of BRC. The inhibitory effect of BRC on pilocarpine yawning was reversed by sulpiride (20 mg/kg). alpha-Methyl-p-tyrosine (alpha-MPT; 100 and 200 mg/kg) did not affect physostigmine yawning but diminished pilocarpine yawning. Furthermore, physostigmine (0.2 mg/kg) inhibited apomorphine (4.0 mg/kg)-induced hyperlocomotion and sniffing but not licking and biting, whereas pilocarpine (4.0 mg/kg) had the opposite effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Continued growth of a large pituitary prolactinoma despite high dose bromocriptine

International Journal of Clinical PracticeVolume 41, Issue 4 p. 712-713 Case Report Continued growth of a large pituitary prolactinoma despite high dose bromocriptine P Bannister MB, MRCP, P Bannister MB, MRCP Department of Medicine, Seacroft Hospital, LeedsSearch for more papers by this authorP Sheridan MB, MRCP, P Sheridan MB, MRCP Department of Medicine, Seacroft Hospital, LeedsSearch for more papers by this author P Bannister MB, MRCP, P Bannister MB, MRCP Department of Medicine, Seacroft Hospital, LeedsSearch for more papers by this authorP Sheridan MB, MRCP, P Sheridan MB, MRCP Department of Medicine, Seacroft Hospital, LeedsSearch for more papers by this author First published: 01 April 1987 https://doi.org/10.1111/j.1742-1241.1987.tb08099.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume41, Issue4April 1987Pages 712-713 RelatedInformation