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Titolo:
Seizure activity and hyperthermia potentiate the increases in dopamine andserotonin extracellular levels in the Amygdala during exposure to d-amphetamine
Autore:
Tor-Agbidye, J; Yamamoto, B; Bowyer, JF;
Indirizzi:
Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA Natl Ctr Toxicol Res Jefferson AR USA 72079 icol, Jefferson, AR 72079 USA Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA Case Western Reserve Univ Cleveland OH USA 44106 Cleveland, OH 44106 USA
Titolo Testata:
TOXICOLOGICAL SCIENCES
fascicolo: 1, volume: 60, anno: 2001,
pagine: 103 - 111
SICI:
1096-6080(200103)60:1<103:SAAHPT>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT BASOLATERAL AMYGDALA; DORSAL RAPHE NUCLEUS; CAUDATE-PUTAMEN; NEURONAL DEGENERATION; REGIONAL DISTRIBUTION; TYROSINE-HYDROXYLASE; GLUTAMATE RELEASE; PERIRHINAL CORTEX; NERVE-TERMINALS; 5-HT3 RECEPTOR;
Keywords:
seizures; neurotoxicity; amphetamine; amygdala; dopamine; serotonin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Bowyer, JF Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA Natl Ctr Toxicol Res HFT-132 Jefferson AR USA 72079 R 72079 USA
Citazione:
J. Tor-Agbidye et al., "Seizure activity and hyperthermia potentiate the increases in dopamine andserotonin extracellular levels in the Amygdala during exposure to d-amphetamine", TOXICOL SCI, 60(1), 2001, pp. 103-111

Abstract

Behavioral stereotypy, hyperthermia, and convulsive activity produced by exposure to multiple doses of d-amphetamine (AMPH) were related to changes in the extracellular levels of dopamine and serotonin (5-HT) in the amygdala, using the technique of microdialysis in awake and freely moving rats. Hyperactivity and stereotypy, as well as increases in microdialysis dopamine levels ranging from 100-300% of pre-AMPH basal microdialysate levels (BL), occurred during exposure to 3 doses of 2.5 mg/kg (3 x 2.5 mg/kg) AMPH. Threedoses of 5 mg/kg produced a more intense stereotypic behavior as well as hyperthermia, and resulted in large increases in the peak dopamine levels (700% BL) while 5-HT levels were increased to a lesser extent (300% BL). The highest doses tested of 3 x 15 mg/kg produced convulsive activity, seizures, intense stereotypy and hyperthermia with peak microdialysate dopamine (1300% BL) and 5-HT levels (1800% BL) that were 2-fold and 6-fold greater, respectively, than those at the 3 x 5-mg/kg doses. Microdialysate glutamate levels were not changed by AMPH exposure. Rats that did not become hyperthermic when dosed with 15 mg/kg AMPH in a cold environment (10 degreesC) exhibited some hyperactivity and stereotypic behavior, but not overt convulsive behavior. Dopamine and 5-HT levels in these rats were significantly reduced by about 75% and 60%, respectively, compared to the room-temperature group. Inclusion of 2 muM tetrodotoxin (TTX) in the microdialysis buffer significantly reduced the 15-mg/kg AMPH-induced increases in dopamine by 30% and the increase in 5-HT levels by 70% at room temperature. These results indicate that a smaller portion of the dopamine release evoked by doses of AMPH that induce seizure activity is neuronal impulse-dependent while the majorityof 5-HT released is impulse-dependent. Irrespective of impulse activity, the hyperthermia alone markedly potentiated dopamine release but had a lesser effect on 5-HT release. Thus, there are differences in the regulation of dopamine and serotonin release in the amygdala from high doses of AMPH, which are known to produce neurotoxicity. Further studies are necessary to determine the impact of these differences in release on AMPH neurotoxicity.

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Documento generato il 21/01/20 alle ore 00:54:52