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Biomedical subjects

F Petty

Publications and source records attributed to F Petty.

136 records · Page 8Linked to original sources
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Indices of brain beta-adrenergic receptor signal transduction in the learned helplessness animal model of depression.

Both stress response and antidepressant drug action may be mediated by beta-adrenergic receptors (beta AR). Since learned helplessness is a stress-induced animal model of depression, beta AR are relevant to investigate in this model. To date, studies have measured changes in total receptor density (RT), but have not examined more detailed aspects of signal transduction mechanisms such as coupling of the receptor to GS protein. We have investigated brain beta AR coupling in the frontal cortex, hippocampus and hypothalamus of rats exposed to inescapable shock and then tested for learned helplessness, and in both tested and naive controls using [125I]-iodocyanopindolol (ICYP) as the ligand. Both antagonist-saturation and agonist-displacement experiments were conducted, and the specificity for the beta AR was optimized by excluding ICYP binding to 5HT1B receptors. The percentage receptor density in the high-conformational state (%RH) and the ratio of agonist (isoproterenol) dissociation constant from the receptor in the low-/high-conformational states (KL/KH) were used as indices of coupling to GS protein. No significant differences were found between rats developing learned helplessness and non-helpless rats after inescapable stress in any parameter measured in any brain region. In the frontal cortex, exposure to inescapable shock induced beta AR uncoupling from GS protein as suggested by a low KL/KH ratio both in helpless and non-helpless rats but not in either control group. In the hypothalamus, there were trends for higher RL, RT and KL/KH ratio in helpless rats and stressed controls compared to naive controls. These findings suggest that beta AR binding parameters in frontal cortex, hippocampus or hypothalamus did not differentiate between helpless and non-helpless rats. Changes in beta AR coupling observed in these brain regions may reflect effects of stress, which appeared to be region-specific, rather than stress-induced behavioral depression.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Beta-adrenergic receptor changes in learned helplessness may depend on stress and test parameters.

Behavioral deficits following inescapable stress (learned helplessness) may serve as an animal model of depression. Previous studies using foot-shock stress to induce learned helplessness and a bar-press test for the stress-induced behavioral deficit have found increased beta-adrenergic receptor density in the hippocampus of learned helpless rats. We replicated these experiments using a tail-shock stress and the shuttle-box test. In our experiments, rats that developed learned helplessness after inescapable stress did not demonstrate any significant differences in beta-adrenergic receptor density or affinity in the frontal cortex, cerebellum, or hippocampus compared to the nonhelpless rats, nor to the tested control rats. These results suggest that beta-adrenergic receptor changes in learned helplessness may depend on the specific stress and test procedures used.

Animals↗
PubMedDate not supplied

The psychiatric sequelae of civilian trauma.

Much of the literature on the psychiatric consequences of stress has focused on wartime combat trauma. However, traumatic events also frequently occur in civilian life. Controlled studies on the psychiatric effects of noncombat trauma were reviewed and a meta-analysis of these data was conducted. Generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), substance abuse, phobia, and major depressive disorder (MDD) were significantly elevated compared with a pooled control group, whereas panic disorder and dysthymic disorder were not significantly increased. These data suggest that the psychiatric effects of civilian trauma include both anxiety and depressive disorders. The results are strikingly similar to those reported in combat veterans, suggesting that severe trauma, even in very different populations, may be associated with similar psychopathology.

Anxiety Disorders↗
PubMedDate not supplied

Serotonin and learned helplessness: a regional study of 5-HT1A, 5-HT2A receptors and the serotonin transport site in rat brain.

Serotonin (5-HT) plays a central role in the neurochemistry of the learned helplessness animal model of depression. Using quantitative autoradiography, we measured the density of 5-HT1A and 5-HT2A receptors and of 5-HT transport sites in medial prefrontal cortex, dorsal hippocampus, septum, hypothalamus, and amygdala in learned helpless rats, and in rats that were nonhelpless after inescapable stress, as well as in shuttlebox-tested and nonhandled controls. We found no changes in 5-HT1A receptor density among the groups in any region studied. In dorsal hippocampus, 5-HT2A receptor density was decreased in nonhelpless rats, while in amygdala 5-HT2A receptor density was decreased in both groups of stressed rats, whether helpless or nonhelpless. In the hypothalamus 5-HT2A receptor density, was decreased in helpless rats as compared to controls. In medial prefrontal cortex, the serotonin transport sites showed decreased density in helpless rats as compared to controls but not to nonhelpless rats. These findings further highlight the complexity of regional 5-HT effects in the learned helplessness animal model.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMedDate not supplied

Adrenergic receptor function in panic disorder. II. Neutrophil beta 2 receptors: Gs protein coupling, effects of imipramine treatment and relationship to treatment outcome.

Panic attacks are associated with increased autonomic symptoms, suggesting increased beta 2-adrenergic receptor (beta 2AR) function in PD. Tricyclic antidepressants downregulate beta AR function. Previous studies on beta AR function in PD, however, are inconsistent. We recently found increased beta AR coupling and density in neutrophils of symptomatic drug-free PD patients. This study evaluated beta AR coupling to Gs protein in 28 controls, 25 drug-free PD patients and 8 PD imipramine-treated patients. PD patients had significantly higher coupling and receptor density, particularly in the high-conformational state. Differences were more pronounced in patients with less depressive symptomatology. Treatment with imipramine was associated with decreased beta AR coupling and density in the high-conformational state. Several beta AR binding parameters were related to severity of anxiety symptoms and treatment outcome. Antidepressants downregulate beta AR density and induce uncoupling from Gs protein in PD. Future studies may investigate beta AR coupling in relationship to treatment outcome and the role of beta AR kinase in PD.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Efficacy of divalproex vs lithium and placebo in the treatment of mania. The Depakote Mania Study Group.

OBJECTIVE: To compare the effectiveness of divalproex sodium with that of lithium and placebo in patients with acute mania. DESIGN: Randomized, double-blind, parallel-group study of treatment outcomes in patients with manic-depressive illness. PATIENTS: A total of 179 hospitalized, acutely manic patients meeting the Research Diagnostic Criteria for manic disorder, approximately half of whom had been nonresponsive to lithium previously, were studied at nine university-affiliated hospitals. INTERVENTIONS: After a minimum 3-day washout period, random assignment for 21 days to divalproex, lithium, or placebo in a 2:1:2 ratio. Dosage of divalproex and lithium was increased if tolerated to a target concentration of 1041 mumol/L (150 micrograms/mL) or 1.5 mmol/L (conventionally expressed as milliequivalents per liter), respectively. MAIN OUTCOME MEASURES: Primary outcome measures were changes in the Mania Rating scale derived from the Schedule for Affective Disorders and Schizophrenia. RESULTS: Intent-to-treat analysis for efficacy was based on data from 68, 35, and 73 patients in the divalproex, lithium, and placebo groups, respectively. Groups were initially comparable except that all eight patients with four or more manic episodes in the previous year were in the divalproex group. In 30%, 33%, and 51% of the above groups, treatment was prematurely terminated due to lack of efficacy, with fewer premature terminations from divalproex than placebo (P = .017). The proportions of patients improving at least 50% were higher for divalproex and lithium groups than for the placebo group: 48% for divalproex (P = .004) and 49% for lithium (P = .025) vs 25% for placebo. Divalproex was as effective in rapid-cycling manic patients as in other patients. CONCLUSIONS: Both divalproex and lithium were significantly more effective than placebo in reducing the symptoms of acute mania. The efficacy of divalproex appears to be independent of prior responsiveness to lithium.

Acute Disease↗