Effects of Some Psychoactive Agents on Prolactin Secretion in Rats of Different Endocrine States

Ja, Clemens; Cj, Shaar; Eb, Smalstig; Matsumoto, C.

doi:10.1055/s-0028-1093870

Cited by 14 publications

(3 citation statements)

References 5 publications

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“…Increased prolactin levels occur in blood from humans (25,31,48), rats (3,4,26,46), and mice (42,43) administered phenothiazines including chlorpromazine. The magnitude of the increase in blood prolactin levels was generally higher in females than males (3,4,25,31,42). Immature, ovariectomized mice administered a single subcutaneous dose of estradiol followed by 9 days of oral administration of a phenothiazine including chlorpromazine, exhibited a slight hypertrophy of the mammary gland at the end of dosing (23).…”

Section: Discussionmentioning

confidence: 99%

Toxicity and Carcinogenicity Studies of Chlorpromazine Hydrochloride and p-Cresidine in the p53 Heterozygous Mouse Model

Petruska¹,

Frank²,

Freeman

et al. 2002

Toxicol Pathol

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The carcinogenic potential of chlorpromazine hydrochloride, a psychotropic agent, was assessed in the p53 heterozygous mouse assay. In a 4-week dose range finding study in p53 wild-type mice, doses of 20,40, 60, and 80 mg/kg were poorly tolerated because of mortality secondary to the severe sedative and hypotensive effects of chlorpromazine. Based on 40% mortality at a dose of 20 mg/kg in the dose-range finding study, a high dose of 10 mg/kg was chosen for the 26-week carcinogenicity study in p53 heterozygous mice. Doses of 2.5, 5, and 10 mg/kg chlorpromazine hydrochloride were well tolerated in the 26-week study. The administration of chlorpromazine hydrochloride at dose levels up to and including 10 mg/kg to p53 heterozygous and wild-type mice did not result in a dose-related increase in tumor incidence or in the type of tumors seen in comparison to controls. Findings related to the administration of chlorpromazine in the 26-week study were limited to minimal uterine and ovarian atrophy in p53 wild-type mice dosed with 10 mg/kg chlorpromazine hydrochloride. However, p53 heterozygous mice administered 400 mg/kg p-cresidine, a genotoxic carcinogen commonly used as a positive control for this model, developed urinary bladder tumors. Administration of p-cresidine also resulted in a regenerative anemia, splenic and hepatic hemosiderosis, renal findings, and ovarian and uterine atrophy. This study demonstrated that chlorpromazine hydrochloride, at the doses tolerated, was not carcinogenic in the p53 heterozygous mouse assay.

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Section: Discussionmentioning

confidence: 99%

Toxicity and Carcinogenicity Studies of Chlorpromazine Hydrochloride and p-Cresidine in the p53 Heterozygous Mouse Model

Petruska¹,

Frank²,

Freeman

et al. 2002

Toxicol Pathol

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“…Blockade of DA receptors by haloperidol resulted in dose-related increases in blood PRL levels and tended to reduce circulating levels of TSH but blocked the ability of apomorphine to inhibit the release of either hormone. These observations support the view that DA mediates an inhibitory influence over PRL release [Hokfhlt and F uxe, 1972;Meites, 1973;Ojeda el al., 1974;Clemens et al, 1974] and exerts an inhibitory action on TSH release. The ability of apomorphine (at doses tested) to suppress TSH release in euthyroid animals was eliminated when TSH was highly elevated by thyroid ectomy; however, the capacity of apomorphine to reduce serum PRL levels was not affected by throidectomy.…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Dopamine Agonists and Haloperidol on Release of Prolactin, Thyroid Stimulating Hormone, Growth Hormone and Luteinizing Hormone in Rats

et al. 1976

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The dose-response effects of apomorphine and ET-495 (piribedil), 2 specific dopamine (DA) receptor stimulators, and haloperidol, a DA receptor blocker, were tested on the secretion of prolactin (PRL), thyroid stimulating hormone (TSH), growth hormone (GH) and luteinizing hormone (LH) in male rats. Both apomorphine and piribedil reduced serum PRL and TSH levels, stimulated GH release at low but not at high doses and either had no effect or tended to reduce serum LH levels. The minimal effective dose of apomorphine for reducing PRL by 30 min was 0.01 mg/kg; TSH inhibition was observed with a dose of 0.1–0.3 mg/kg. The inhibitory effects of apomorphine (1.0 mg/kg) on PRL and TSH levels were maximal by 15 min and diminished by 120 min; plasma GH was highest 120 min after injection. Thyroidectomy (10 days) markedly elevated serum TSH, had no effect on serum PRL and inhibited the ability of apomorphine (0.1 or 0.3 mg/kg) to reduce TSH but not PRL levels. These observations may indicate that separate dopaminergic control mechanisms exist for TSH and PRL secretion. Administration of haloperidol elevated serum PRL, tended to lower TSH, dramatically reduced GH and had no effect on LH levels. Haloperidol pre-treatment blocked the effects of apomorphine on PRL, TSH and GH secretion. The overall results of this study indicate that DA agonists inhibit PRL and TSH, stimulate GH but do not stimulate LH release in male rats.

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“…Hyperprolactinemia is potentially associated with amenorrhoea, galactorrhoea, sexual dysfunction, 44 breast engorgement, and osteoporosis. 37 , 45 Neuroscientists began investigations into prolactin levels as an indicator of hypothalamic activity during psychiatric illness 19 and following the observation in animals that many antipsychotics stimulate prolactin secretion 46 , 47 consistent with prolactin levels being an indicator of dopamine blockade and generating the hypothesis that increased serum prolactin levels were associated with antipsychotic clinical efficacy. However, prolactin levels are inconsistently correlated to efficacy; for example clozapine is the most efficacious antipsychotic, but it does not cause a sustained increase in prolactin levels ( Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

Review of serum prolactin levels as an antipsychotic‐response biomarker

Gault

Nussbaum

2018

OAJTMR

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Antipsychotics acting as antagonists at dopamine D2 receptors concentrated in the striatum are the cornerstone of effective treatment of psychosis. Substantial progress in treating persons with schizophrenia could be achieved by the identification of biomarkers which reliably determine the lowest efficacious dose of antipsychotics. Prolactin levels have been considered a promising treatment-response biomarker due to dopamine's regulation of serum prolactin levels through D2 receptors in the hypothalamic-pituitary pathway. Prolactin secretion in response antipsychotic administration is associated with the antipsychotics affinity for D2 receptors. This review assesses the available literature on the use of serum prolactin levels as an antipsychotic-response biomarker. Articles were identified through PubMed as well as the reference lists of full text articles available online. Relevant publications were summarized briefly to define the limitations and utility of serum prolactin levels as a tool for improving antipsychotic dosing. Serum prolactin levels in combination with prolactin-inducing potencies for each antipsychotic may help identify the lowest effective dose of antipsychotic medications. , In addition to the fact that prolactin secretion is dependent on serum antipsychotic levels and not brain levels, recent findings show that prolactin release is independent of the β-arrestin-2 pathway and GSK3β regulation, one branch of the pathway that has been implicated in antipsychotic efficacy. Therefore, serum prolactin is an indirect biomarker for treatment response. Further investigations are warranted to characterize prolactin-antipsychotic dose-response curves and systematically test the utility of measuring prolactin levels in patients to identify a person's lowest efficacious dose.

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Effects of Some Psychoactive Agents on Prolactin Secretion in Rats of Different Endocrine States

Cited by 14 publications

References 5 publications

Toxicity and Carcinogenicity Studies of Chlorpromazine Hydrochloride and p-Cresidine in the p53 Heterozygous Mouse Model

Toxicity and Carcinogenicity Studies of Chlorpromazine Hydrochloride and p-Cresidine in the p53 Heterozygous Mouse Model

Differential Effects of Dopamine Agonists and Haloperidol on Release of Prolactin, Thyroid Stimulating Hormone, Growth Hormone and Luteinizing Hormone in Rats

Review of serum prolactin levels as an antipsychotic‐response biomarker

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