Biomedical subjects

S Novotney

Publications and source records attributed to S Novotney.

3 recordsLinked to original sources

PubMed1995

Short-term and long-term effects of p-chloroamphetamine on hippocampal serotonin and corticosteroid receptor levels.

Hippocampal corticosteroid receptors are regulated by corticosterone as well as by neurotransmitters, such as serotonin (5-HT). Studies have demonstrated that long-term changes in 5-HT levels are associated with alterations in hippocampal glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) number. However, the effect of short-term manipulations of 5-HT levels on hippocampal corticosteroid receptor levels has not been thoroughly investigated. The present set of studies examined the effect of para-chloroamphetamine (PCA) administration on both short-term and long-term regulation of hippocampal 5-HT and corticosteroid receptor levels. PCA is a selective serotonergic neurotoxin which initially releases 5-HT to cause a short-term depletion of 5-HT stores, followed by a long-term decrease in 5-HT levels which presumably reflects the destruction of 5-HT nerve terminals. In the initial study rats were adrenalectomized and 24 h later injected with PCA (20 mg/kg) and sacrificed 3 h later. PCA produced a large decrease in hippocampal 5-HT (-79%) and 5-hydroxyindoleacetic acid (5-HIAA) (-40%) concentrations. In addition, PCA significantly decreased both hippocampal GR (-28%) and MR (-35%) levels. Pretreatment with fluoxetine (20 mg/kg), which presumably blocks the uptake of PCA into 5-HT nerve terminals, completely blocked the PCA-induced decreases in both 5-HT and corticosteroid receptor concentrations. In a final experiment, the long-term (7 days) effect of PCA administration on hippocampal 5-HT and corticosteroid receptor levels was examined. PCA (10 mg/kg given on 2 consecutive days) was administered to adrenal-intact rats which were adrenalectomized 6 days later and subsequently sacrificed following a 24 h interval. PCA produced an 87% decrease in hippocampal 5-HT and 5-HIAA levels, but did not alter hippocampal GR or MR levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

PubMed1994

Methamphetamine-induced decrease in neural glucocorticoid receptors: relationship to monoamine levels.

Methamphetamine (MA) is a potent psychostimulant drug which is neurotoxic to dopamine (DA) and serotonin (5-HT) neurons. It has been previously reported that acute MA administration to adrenalectomized rats produced large dose-related decreases in hippocampal and striatal glucocorticoid receptors (GR). The present study was designed to determine if MA could decrease neural and peripheral GR when administered to adrenal-intact rats using a neurotoxic dosing regimen which produces depletions of brain DA and 5-HT levels. MA (0, 6.25, 12.5 and 25 mg/kg) was administered to adrenal-intact rats every 2 h for a total of 4 doses. Rats were adrenalectomized (ADX) 6 days later and subsequently sacrificed 24 h later. GR and mineralocorticoid receptors (MR) were measured using radioligand binding assays. Tissue levels of 5-HT and DA were measured in order to confirm the neurotoxic effects of MA and also to relate corticosteroid receptor levels to monoamine concentrations. MA produced dose-related decreases in GR levels in the hippocampus, striatum, frontal cortex and hypothalamus. Hippocampal MR were not affected by MA. 5-HT was also decreased in all of these same 4 brain regions, whereas DA was significantly decreased only in the striatum. MA did not decrease GR in cerebellum and similarly had no effect on DA and 5-HT in this region. MA also did not decrease GR or 5-HT levels in the spleen. These results demonstrate that MA produces a decrease in GR in a variety of brain areas, which is related primarily to 5-HT depletions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

PubMed1994

Adrenalectomy attenuates kainic acid-induced spectrin proteolysis and heat shock protein 70 induction in hippocampus and cortex.

Glucocorticoids have been shown to exacerbate the damaging effects of a variety of neurotoxic insults in the hippocampus and other brain areas. Evidence suggests that the endangering effects of glucocorticoids may be due to augmenting the cascade of events, such as elevations in intracellular calcium levels, because of excitatory amino acid (EAA) receptor stimulation. A potential mechanism responsible for EAA-induced neuronal damage is activation of calcium-sensitive proteases, such as calpain, which then proteolytically degrade cytoskeleton structural proteins, such as spectrin. The present study was designed to determine if glucocorticoids can regulate the spectrin proteolysis produced by the EAA agonist, kainic acid. Rats were adrenalectomized (ADX) or sham operated and 7 days later injected with kainic acid (10 mg/kg). Twenty-four hours later rats were killed and tissues obtained for western blot analyses of the intact spectrin molecule and the proteolytically derived breakdown products. Kainic acid produced an approximate sevenfold increase in the 145-155-kDa spectrin breakdown products in the hippocampus relative to ADX or sham rats injected with vehicle. ADX attenuated the kainic acid-induced increase in breakdown products by 43%. In a similar way, kainic acid produced a large 10-fold increase in spectrin breakdown products in the frontal cortex, which was also significantly attenuated (-80%) by ADX. Induction of heat shock protein 70 (hsp70) by neurotoxic insults has been suggested to be a sensitive indicator of cellular stress in neurons. Kainic acid induced large amounts of hsp70 in both hippocampus and frontal cortex of sham-operated rats that was markedly attenuated (85-95%) by ADX.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗