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Biomedical subjects

K Y Little

Publications and source records attributed to K Y Little.

13 recordsLinked to original sources
PubMed1992

Autoradiographic characterization of [3H]imipramine and [3H]citalopram binding in rat and human brain: species differences and relationships to serotonin innervation patterns.

The neuroanatomical distribution of binding sites for [3H]imipramine and [3H]citalopram was assessed by in vitro autoradiography in select regions of the rat and human forebrain. To determine involvement of serotonin-containing terminals in the binding of [3H]imipramine and [3H]citalopram, binding of these compounds was measured in rats after destroying serotonin-containing neurons with 5,7-dihydroxytryptamine (5,7-DHT). Treatment with this neurotoxin decreased serotonin content by 90% and reduced [3H]citalopram binding to a similar extent. These results demonstrate that [3H]citalopram binding is a reliable marker for serotonin-containing terminals. Binding of [3H]imipramine was reduced by only 15-35% after 5,7-DHT treatment. These latter results suggest that only a small fraction of [3H]imipramine binding to brain sections is associated with serotonergic terminals under standard conditions used in autoradiographic studies with the ligand. Dose-response effects of fluoxetine and desipramine on displacement of [3H]imipramine binding in forebrain regions indicate that the ligand labels predominantly high capacity, low affinity binding sites. To determine the utility of the rat brain as a model for [3H]imipramine and [3H]citalopram binding in the human brain, binding of the ligands was compared in human and rat hypothalamus, amygdala, and hippocampus. The pharmacological characteristics of [3H]imipramine and [3H]citalopram binding were similar in the rat and human brain. However, substantial species differences were observed in topographic patterns of [3H]imipramine binding within the hippocampus and hypothalamus. The distribution of [3H]citalopram binding sites within the amygdala and hypothalamus were also strikingly different in rats compared to humans. This work provides the first demonstration that marked species differences exist in the topography of serotonergic innervation and in the distribution of [3H]imipramine binding sites within the rat and human brain regions examined.

5,7-Dihydroxytryptamine↗
PubMed1992

Beta-adrenergic receptor binding in human and rat hypothalamus.

Quantitative autoradiographic analysis of beta-adrenergic binding sites was conducted in human postmortem hypothalamus using the radioligand 125I-pindolol. The focus was on the hypothalamic nuclei most clearly involved in corticotropin-releasing hormone (CRH) release, the PVN and SON. For comparison, the distribution of hypothalamic beta-adrenergic receptors was evaluated in the rat. A high level of beta-adrenergic receptor binding was found in the human paraventricular nucleus (PVN) and supraoptic nucleus (SON), but not in the rat. The majority of the beta-adrenergic receptors found in the human hypothalamus were of the beta 2-subtype. In contrast, in the rat hypothalamus, the majority of receptors were of the beta 1-subtype. These results show that the anatomical loci exist for direct beta-adrenergic influence on hypothalamic neuroendocrine function in the human and that the topography of beta-adrenergic receptors is markedly different in the rat and human hypothalamus.

Adult↗
PubMed1991

Beta-adrenergic receptor distribution in human and rat hippocampal formation: marked species differences.

The topography of beta-adrenergic receptors in the rat and human hippocampal formation was assessed by in vitro binding of 125I-pindolol to tissue sections. Marked differences were found in the distribution of beta-adrenergic receptors and in the relative amounts of beta 1 and beta 2 receptor subtypes in the two species. In the human, the highest receptor densities were present in the pyramidal cell layer and in the stratum lacunosum-moleculare. In the rat hippocampus, those regions contained the lowest densities of 125I-pindolol binding sites. The highest densities of beta-adrenergic receptors in the rat hippocampal formation were found in the ventral subiculum and in the entorhinal cortex. In contrast, in the human hippocampus, the subiculum and entorhinal cortex contained relatively low densities of the receptors. Competition studies with beta 1- and beta 2-selective antagonists revealed that beta 2-adrenergic receptors predominate in the human hippocampus and beta 1-adrenergic receptors predominate in the rat hippocampus. The marked species differences observed suggest that the pharmacological responsivity of the hippocampus to adrenergic agents and the role of noradrenaline in regulation of hippocampal function could be very different in rats compared to humans.

Animals↗
PubMed1991

Dose-response studies with thyrotropin-releasing hormone (TRH) in abstinent male alcoholics: evidence for selective thyrotroph dysfunction?

A reduced thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) has been reported in subjects with a history of alcoholism whereas prolactin (PRL) responses have generally been normal. One hypothesis proposed to explain the reduced TSH response is down-regulation of pituitary TRH receptors. If this is correct, PRL response should also be diminished. To account for the different dose-response characteristics of TSH/PRL we have given four dosages of TRH (25, 100, 500 and 800 micrograms) to eight noncirrhotic, male alcoholics abstinent from ethanol a minimum of 28 days and to seven male control subjects. Across the TRH dose range the alcoholic subjects exhibited reduced basal TSH (p = .01) and a reduced TSH response (p = .0023) but no differences in basal and stimulated PRL levels. Alcoholic subjects had higher basal T4, T3 and FT4I values than did control subjects but covarying for T4, T3 and FT4I did not change the significance of either TSH or PRL findings. No significant differences in estradiol, estrone, testosterone, cortisol or glucose were noted between groups. The present study confirms the observation of a lower TSH response to TRH in abstinent alcoholics and indicates that the lower response cannot be overcome by increasing TRH dosage. The similar PRL response between groups suggests normal lactotroph function in noncirrhotic abstinent alcoholics and argues against the pituitary TRH receptor down-regulation hypothesis.

Adult↗
PubMed1990

Altered pineal serotonin binding in some suicides.

Serotonergic abnormalities have been regularly reported in the brains of suicide victims. Because of evidence that pineal function is altered in depressed subjects and that serotonin-releasing axons may innervate the pineal, we assayed tritiated serotonin binding in a series of control and suicide pineals. High affinity binding was present, and there were apparent differences between some suicides and controls.

Adult↗
PubMed1990

Increased detection of elevated TSH using immunoradiometric assay.

Using a highly sensitive immunoradiometric assay, the authors detected an increased rate of elevated thyrotropin in 2,099 patients vs 1,789 patients examined with radioimmunoassay. Closer scrutiny of mood disorder patients with elevations found confirmatory evidence of thyroid dysfunction in most.

Feeding and Eating Disorders↗
PubMed1990

Brain markers and suicide: can a relationship be found?

Recent work suggests that some persons who commit suicide have altered neurochemistry in their brains. It remains unclear which of the many reported abnormalities are most reliably present and whether they reflect a specific psychiatric disorder or a disposition to violent impulsivity. A number of technical and interpretive problems must be clarified, but a postmortem test indicating that a subject was at high risk for suicide may eventually emerge. This approach would not be useful for ruling out suicide, since altered neurochemistry is not likely to be involved in every case.

Brain Chemistry↗
PubMed1989

Predictors of response to high dose antipsychotics in chronic schizophrenics.

Significant numbers of chronic schizophrenic patients do not experience sufficient symptom relief from usual doses of antipsychotic medication. Clinicians must decide if high doses of antipsychotics should be tried. In this study baseline symptoms, drug levels, and the symptomatic effects of an acute stimulant challenge were examined before 14 subjects received a 50% increase in their antipsychotic dosing. The group as a whole did not improve. Several individuals with lower drug levels, high baseline hallucinations, and stimulant-induced improvement in hallucinations improved mildly after 3 weeks on the higher antipsychotic dose.

Adult↗
PubMed1988

Lack of acute d-amphetamine effects on thyrotropin release.

Case reports have suggested that amphetamine abuse causes excessive secretion of thyrotropin (TSH) and thyroxine (T4). Such an amphetamine-induced effect might be noradrenergic-mediated in the hypothalamus. The current controlled study examined oral d-amphetamine effects on the hypothalamic-pituitary-thyroid axis in normal humans. No acute effects were seen on TSH, T3 or T4 levels. d-Amphetamine elevated cortisol levels at 180 min, as previously reported.

Adult↗
PubMed1988

Amphetamine, but not methylphenidate, predicts antidepressant efficacy.

Several researchers have explored the possibility that acute stimulant response may predict eventual improvement after specific antidepressants. This review analyzes the relationship between stimulant response and nonspecific antidepressant response. In five studies, amphetamine responders were found to eventually improve after antidepressant treatment in 85% of the cases, while nonresponders improved in 43% of the cases. In contrast, acute methylphenidate responders and nonresponders eventually improved on antidepressants at equivalent rates. Amphetamine sensitivity appears to be a trait (possibly pharmacodynamic) that is independent of depressive illness but predictive of tricyclic responsiveness. Other evidence has suggested that amphetamine and methylphenidate cause similar behavioral and symptomatic effects through distinct mechanisms of potential clinical relevance. The most effective method for administering an amphetamine challenge and its appropriate clinical use remain unclear.

Amphetamine↗