Apomorphine-induced Growth Hormone Secretion Research Articles

Psychopathological and behavioral correlates of dopaminergic sensitivity in alcohol-dependent patients.

To explore 2 facets of dopamine receptor sensitivity in alcoholics: (1) whether reduced sensitivity of central dopamine receptors is correlated with anxiety, depression, or novelty seeking and (2) whether this reduction is associated with poor treatment outcome. Sixty-four alcohol-dependent patients were assessed according to their clinical outcome, sensitivity of central dopamine receptors (apomorphine-induced growth hormone secretion), mood states, and personality traits before and after detoxification. Patients with poor treatment outcome displayed a blunted growth hormone response before, but not after, detoxification. Growth hormone response was not significantly correlated with novelty seeking. Relapsing patients tended to be less depressed than patients who remained abstinent during observation. This study did not support the hypothesis that reduced sensitivity of dopamine receptors is associated with anxiety, depressed mood, or high novelty seeking in alcoholism.

Evidence for prolonged recovery of dopaminergic transmission after detoxification in alcoholics with poor treatment outcome.

It has been hypothesized that dysfunction of dopaminergic neurotransmission is involved in the pathogenesis of alcohol addiction. Therefore, peripheral dopamine levels, sensitivity of central dopamine receptors (apomorphine-induced Growth Hormone (GH) secretion), and the inhibitory efficacy of G-proteins on adenylyl cyclase activity (as an indicator for dopamine D2-receptor coupled second messenger mechanisms) were measured in 45 alcohol-dependent patients before and after detoxification and in 10 healthy controls. The time needed to adjust to abstinence conditions differed between patients with good and poor treatment outcome. In subsequent abstainers, effects of alcohol withdrawal were already found during the first 24 hours of abstinence (normalisation of GH response, increases in dopamine levels and the inhibitory efficacy of G-proteins). During the next 7 days of abstinence, no more significant changes were observed in the assessed variables. In subsequent relapsers, no significant effect of acute ethanol withdrawal on the same measures was found. However, at day 8 of abstinence, increases in apomorphine-induced GH secretion (towards normalisation), in dopamine plasma levels, and in the inhibitory efficacy of G-proteins (towards above-normal levels) were observed. This retarded adjustment of dopaminergic signal transduction seems to reflect the relapse risk of treatment nonresponders.

CCK-8 antagonizes apomorphine-induced growth hormone secretion in normal subjects.

Cholecystokinin octapeptide (CCK-8) (5 ug iv over 10 minutes) administered to normal men had no effect on basal growth hormone (GH) or prolactin secretion but significantly antagonized the GH response to the dopamine (DA) receptor agonist, apomorphine HCI (Apo) (0.5 mg sc), 30 (P less than 0.05) and 45 minutes (P less than 0.01) after Apo injection (n = 8). These results are compatible with an inhibitory effect of CCK-8 on certain DA mechanisms in the hypothalamic-pituitary axis. Whether CCK-8 affects DA function in other brain regions in man is unknown.

Advances in medical social science, vol. 1

1.Interpretation of neuroendocrine studies in schizophrenia requires consideration of (a) the large number of variables that affect drug-induced endocrine responses (b) the effect of prior neuroleptic therapy (c) heterogeneity of schizophrenia (d) heterogeneity of receptors (e) uniqueness of the hypothalamic-pituitary axis (f) selectivity and pharmacokinetics of administered drugs.2.Apomorphine increases growth hormone secretion by an effect on dopamine receptors that are not linked to adenylate cyclase and which are located outside the blood brain barrier.3.Hypothalamic-pituitary histaminergic H2 and α-adrenergic function are unchanged in chronic schizophrenia.4.Schizophrenic symptoms persist despite complete blockade of dopamine receptors modulating prolactin secretion.5.Studies on dopamine receptors modulating prolactin secretion are unlikely to shed light on the pathophysiology of schizophrenia.6.Screening for drugs which block apomorphine-induced growth hormone secretion but do not increase prolactin may provide a way of detecting anti-schizophrenic drugs which are devoid of side effects associated with hyperprolactinemia and which do not induce parkinsonism or tardive dyskinesia.

CCK-33 antagonizes apomorphine-induced growth hormone secretion and increases basal prolactin levels in man

Cholecystokinin (CCK-33) (225 Ivy Dog Units intravenously) had no effect on basal growth hormone (GH) secretion but antagonized the GH response to the dopamine receptor agonist, apomorphine HCl (0.5 mg sc) (N = 7), and induced a transient increase in basal prolactin (PRL) secretion (N = 8) in normal men. These findings are similar to those desoribed with neuroleptics and are compatible with an inhibitory effect of CCK-33, or fragments, on dopamine function in man, at least in the hypothalamic-pituitary axis. However, an inhibitory effect of CCK-33 on the release of GH and a stress-induced increase in PRL secretion cannot be excluded.

Apomorphine induced growth hormone secretion in anorexia nervosa

(1) Five female in-patients suffering from anorexia nervosa of moderate-severe degree were given the dopamine receptor agonist apomorphine. The growth hormone (GH) secretion induced by this stimulation was measured and the results compared with those of age-matched healthy female controls. (2) In contrast to most previous reports we failed to demonstrate elevated basal levels of GH in the anorectic group compared to the controls. (3) None of the anorectic patients showed any increase in GH values after apomorphine compared to 5 out of 9 controls. It is concluded that the failure to respond is not dependent on a high basal level of GH. (4) Our results lend support to the notion that there may be some abnormality in hypothalamic function possible involving dopamin receptor activity in anorexia nervosa.Jan Wglinder, M.D., Ph.D., Professor, Department of Psychiatry, University Hospital, University of Linkoping, S-581 85 Linkoping SwedenJan Balldin, M.D., Ph.D., Consultant, Department of Psychiatry and neuroch...

Effect of CCK-33 on prolactin and apomorphine-induced growth hormone secretion in man.

Effect of CCK-33 on prolactin and apomorphine-induced growth hormone secretion in man.

Neuroendocrine evaluation of CCK-peptides on dopaminergic function in man

1. 1. CCK-33 (225 Ivy Dog Units iv) antagonized the growth hormone response to the dopamine receptor agonist, apomorphine HCl (0.5 mg sc), and increased basal prolactin secretion in normal male volunteers. A stress mediated prolactin effect could not be excluded. 2. 2. CCK-8 (5 ug iv) antagonized the growth hormone response to apomorphine but had no effect on basal prolactin or plasma homovanillic acid. 3. 3. Ceruletide (0.3 ug/kg im) had no effect on basal prolactin or apomorphine-induced growth hormone secretion. 4. 4. CCK-33, CCK-8 and ceruletide had no effect on basal growth hormone secretion which suggests that they do not inhibit the release of growth hormone. 5. 5. These findings are compatible with an inhibitory effect of CCK-33 and CCK-8 (or fragments) on dopaminergic function in man, at least in the hypothalamic-pituitary axis and point to a simple way to study the effect of peptides on dopaminergic function in man including those which may not cross the blood brain barrier.

Effect of sulpiride, an atypical neuroleptic, on apomorphine-induced growth hormone secretion

NAIR, N. P. V., S. LAL, H. I. ISKANDAR, P. ETIENNE, P. L. WOOD AND H. GUYDA. Effect of sulpiride, an atypical neuroleptic, on apomorphine-induced growth hormone secretion. BRAIN RES. BULL. 8(6) 587–591, 1982.—Sulpiride (100 mg IM), an atypical neuroleptic, which does not block dopamine (DA) receptors that are linked to adenylate cyclase, abolished the growth hormone (GH) response to the DA receptor agonist, apomorphine (Apo) HC1 (0.5 mg SC) in seven healthy male subjects. These results suggest that Apo increases GH secretion in man by an effect on DA receptors that are not linked to adenylate cyclase.

Effect of domperidone on apomorphine-induced growth hormone secretion in normal men.

Domperidone, a peripheral dopamine (DA) receptor blocker which poorly crosses the blood-brain barrier and which is inactive towards dopamine-sensitive adenylate cyclase, in a dose (100 micrograms/kg) sufficient to increase serum prolactin levels at least 5-fold, decreased the growth hormone (GH) response to the DA receptor agonist, apomorphine HCI (Apo) (0.5 gm s.c.) in each of six normal men examined. The mean GH increment at 30, 45, 60 and 75 min following Apo injection, the mean individual peak increment and the mean individual GH secretion (ng min) was significantly decreased by domperidone pretreatment (p less than 0.005 -p less than 0.002). These results indicate that in man Apo stimulates GH secretion by an effect on DA receptors which are not linked to adenylate cyclase and which are situated at a locus in the hypothalamic-pituitary axis that lies outside the blood-brain barrier.

Drug-induced growth hormone and prolactin responses in schizophrenia research

1. Interpretation of neuroendocrine studies in schizophrenia requires consideration of (a) the large number of variables that affect drug-induced endocrine responses (b) the effect of prior neuroleptic therapy (c) heterogeneity of schizophrenia (d) heterogeneity of receptors (e) uniqueness of the hypothalamic-pituitary axis (f) selectivity and pharmacokinetics of administered drugs. 2. Apomorphine increases growth hormone secretion by an effect on dopamine receptors that are not linked to adenylate cyclase and which are located outside the blood brain barrier. 3. Hypothalamic-pituitary histaminergic H2 and alpha-adrenergic function are unchanged in chronic schizophrenia. 4. Schizophrenic symptoms persist despite complete blockade of dopamine receptors modulating prolactin secretion. 5. Studies on dopamine receptors modulating prolactin secretion are unlikely to shed light on the pathophysiology of schizophrenia. 6. Screening for drugs which block apomorphine-induced growth hormone secretion but do not increase prolactin may provide a way of detecting anti-schizophrenic drugs which are devoid of side effects associated with hyperprolactinemia and which do not induce parkinsonism or tardive dyskinesia.

Effect of L-tryptophan on apomorphine-induced growth hormone secretion in normal subjects.

Oral administration of the serotonin precursor, L-tryptophan, to normal male volunteers (n = 7) in a dose (3 g) sufficient to increase free plasma tryptophan concentrations more than 12-fold had no significant effect on basal growth hormone secretion or on apomorphine HCL-induced (0.75 mg sc) peak growth hormone concentrations. These data suggest that, in man, tryptophan administration has little effect on central dopaminergic function, at least in the hypothalamic-pituitary axis and that serotonergic mechanisms have no major modulatory effect on dopamine-mediated growth hormone secretion.

Effect of Clozapine on Apomorphine-Induced Growth Hormone Secretion and Serum Prolactin Concentrations in Schizophrenia

Clozapine had no effect on basal serum growth hormone concentrations in 10 schizophrenic patients but significantly inhibited the apomorphine-induced growth hormone increase that occurred in 7 subjects. Clozapine caused a slight (17%) but significant elevation in basal serum prolactin levels. These data suggest that in man clozapine, like other neuroleptics, blocks dopamine receptors, at least in the hypothalamic-pituitary axis.

Effect of lithium on hypothalamic-pituitary dopaminergic function.

The effect of lithium on apomorphine-induced growth hormone secretion and haloperidol-induced prolactin secretion was examined in eight male subjects without history of manic-depressive illness. Lithium had no effect on baseline or drug-induced changes in serum growth hormone or prolactin concentrations. These data suggest that lithium does not alter hypothalamic-pituitary dopamine receptor function.

Effect of methysergide and pimozide on apomorphine-induced growth hormone secretion in men.

The dopamine receptor agonist, apomorphine HCl (0.75 mg sc) increased serum growth hormone (GH) concentrations in each of 6 subjects. This increase was not inhibited by pretreatment with the serotonin antagonist, methysergide, but was completely abolished in the 4 individuals pretreated with pimozide, a selective dopamine receptor blocking agent. These results provide further evidence that apomorphine-induced GH secretion is mediated by a dopaminergic mechanism and is independent of a serotonergic mechanism.