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Biomedical subjects

G Koob

Publications and source records attributed to G Koob.

At least 19 recordsLinked to original sources
PubMed2000

Drug addiction.

Explore the source record for details and available documents.

Animals↗
PubMed1999

Structural and compositional determinants of cortistatin activity.

Cortistatin-14 (CST-14) is a putative novel neuropeptide that shares 11 of its 14 residues with somatostatin-14 (SRIF-14), yet its effects on sleep physiology, locomotor behavior and hippocampal function are different from those of somatostatin. We studied the structural basis for cortistatin's distinct biological activities. As with SRIF-14, CST-14 does not show any preferred conformation in solution, as determined by circular dichroism and nuclear magnetic resonance. Synthetic cortistatin analogs were designed and synthesized based on the cyclic structure of octreotide. Biological assays were carried out to determine their binding affinities to five somatostatin receptors (sstl-5) and their ability to produce changes in locomotor activity and to modulate hippocampal physiology and sleep. The results show that the compound with N-terminal proline and C-terminal lysine amide exhibits cortistatin-like biological activities, including reduction of population spike amplitudes in the hippocampal CA1 region, decrease in locomotor activity and enhancement of slow-wave sleep 2. These findings suggest that both proline and lysine are necessary for cortistatin binding to its specific receptor.

Amino Acid Sequence↗
PubMed1997

Anxiolytic activity of NPY receptor agonists in the conflict test.

This investigation examined receptor subtype specificity and possible modulation by GABAa receptor ligands of NPY-induced behavioral responses to stressful stimuli. First, a series of NPY receptor agonists were examined for their potential effects on punished responding in a conflict test modified for incremental shock. NPY, peptide YY (PYY) and NPY Y1 receptor agonists [Leu31,Pro34]-NPY and [Gly6, Glu26,Lys26,Pro34]-NPY produced increases in punished responding in the conflict test. No significant effects on unpunished responding were noted. The pattern of responding was similar to that observed with the benzodiazepine agonist chlordiazepoxide. Neither pancreatic peptide (PP) nor the Y2 agonists NPY13-36 or [Glu2,32,Ala6,Dpr27,Lys28]-NPY significantly altered punished or unpunished responding. Of significance, the atypical Y1 agonist [Cys7,21,Pro34]-NPY produced negligible effects on punished responding, consistent with the presence of a subclass of Y1 receptors. Second, the anxiolytic effects of NPY were subjected to treatments that block actions at the GABAa receptor complex. The increase in punished responding produced by NPY was not altered by administration of the benzodiazepine antagonist flumazenil and only partially blocked by the picrotoxinin receptor ligand isopropylbicyclophosphate (10 and 15 microg/kg). These findings further support the hypothesis that the pharmacologic substrates for the anxiolytic-like actions of NPY may be mediated by the Y1 receptor subtype and suggest that these actions are independent of either the benzodiazepine or picrotoxinin binding sites of the GABA/benzodiazepine receptor complex.

Animals↗
PubMed1996

Viral persistence in neurons alters synaptic plasticity and cognitive functions without destruction of brain cells.

Neurons have a restricted expression of MHC heavy chain molecules which prevents presentation of antigens of infecting viruses. As a result, such infected cells escape immune surveillance and allow the establishment of noncytolytic persistent infection. Here we show that a chronic noncytolytic viral infection both in vitro and in vivo selectively perturbed the expression of GAP-43, a protein that plays a central role in neuronal plasticity processes accompanying learning and memory. GAP-43 expression was greatly decreased in the hippocampus, an area of heightened viral replication, while synaptic density was preserved. Concurrently, the ability to learn tasks was significantly impaired in these persistently infected mice. Yet, infected neurons remained free from structural injury.

Animals↗
PubMed1994

The effects of lisuride on mood and sleep during acute withdrawal in stimulant abusers: a preliminary report.

Psychostimulant abusers often experience anhedonia, depression, fatigue, craving, and hypersomnia and increased propensity for rapid eye movement (REM) sleep during periods of acute and subacute withdrawal from cocaine and amphetamine. These signs and symptoms may reflect a state of relative functional dopamine depletion in the brain during abstinence. Lisuride, which has dopaminergic agonist effects, has been reported to reduce signs of psychostimulant withdrawal in rodent models of stimulant abuse. These observations prompted us to test the effects of oral administration of lisuride for 3 weeks (up to 4.0 mg daily) on mood and craving ratings in a double-blind, parallel design, controlled study in hospitalized stimulant abusers during acute withdrawal from cocaine or amphetamine. Although administration of lisuride significantly prolonged REM latency and reduced REM time, amelioration of other signs of withdrawal was not significantly greater in lisuride as compared with placebo treated patients. Self-rated craving ratings, however, were low in both groups throughout the hospital stay. Further studies, perhaps in patients with more severe symptoms during withdrawal, are needed to fully test the efficacy of lisuride in the treatment of stimulant withdrawal.

Administration, Oral↗
PubMed1990

The influence of cocaine self-administration on in vivo dopamine and acetylcholine neurotransmission in rat caudate-putamen.

Presynaptic dopamine and acetylcholine transmission in the anteroventral (limbic) caudate-putamen were studied by microdialysis in freely moving rats during cocaine self-administration sessions. Acute cocaine exposure elevated dopamine (DA) overflow in drug-naive animals. However, during repeated cocaine administration, the drug-induced elevation of DA was attenuated in animals previously exposed (during the prior 9 days) to cocaine. The diminished dopamine response in repeatedly treated animals while self-administering cocaine was speculated to be due to increased activity of DA transport carrier and/or supersensitive receptors modulating DA release. During repeated cocaine administration, extracellular acetylcholine levels in animals previously exposed to cocaine were found to be significantly decreased compared with controls. The findings of the study may suggest a functional development of supersensitive DA receptors postsynaptic to the DA terminal (located on cholinergic neurons) as a consequence of previous cocaine exposure. Such supersensitivity would allow for a reduced DA signal to be amplified at the postsynaptic level during repeated cocaine self-administration.

Acetylcholine↗
PubMed1976

[Modification of glycylglycine dipeptidase activity in the human ovary using follicle stimulating hormone. I].

The glycyl glycine dipeptidase activity under the in vitro influence of two follicle-stimulating hormone preparations of different concentration was investigated in 36 ovaries. A significant impediment was observed under Folistiman, whereas under Anthrogon the impediment could only be detected with higher concentrations. The FSH/ICSH relation evidently plays an important role in this respect. The results are in support of the statement that the glycyl glycine activity in vivo also depends on the gonadotrophin production. At the same time they affirm the fact that not only endopeptidases play a role in the hormone metabolism of the ovary.

Adnexa Uteri↗