Studies on the changes of neurotransmitters and neuropeptides in the basal ganglia of the rat brain induced by the psychostimulants methamphetamine and cocaine.
Item
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Title
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Studies on the changes of neurotransmitters and neuropeptides in the basal ganglia of the rat brain induced by the psychostimulants methamphetamine and cocaine.
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Identifier
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AAI9917720
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identifier
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9917720
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Creator
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Zhang, Yong.
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Contributor
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Adviser: Jesus A. Angulo
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Date
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1999
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience | Biology, Molecular | Health Sciences, Pharmacology
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Abstract
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Methamphetamine (METH) and cocaine are the most commonly abused psychomotorstimulants. Repeated injections of psychostimulants produce behavioral sensitization. Tyrosine hydroxylase (TH) mRNA levels in the somatodendritic regions and preprotachykinin (PPT) and preproenkephalin (PPE) mRNA levels in the dopaminergic terminal region were measured to evaluate the involvement of striatal neuropeptides in behavioral sensitization. In vivo microdialysis was used to determine if the augmented behavioral response following daily psychostimulant administration was associated with an increase in dopamine and glutamate release in the caudate-putamen (dCPu), nucleus accumbens (NAc), ventral tagmental area (VTA) and substantia nigra compacta (SNc).;TH mRNA level in the VTA was increased at day 15 withdrawal following 6 daily (twice/day) injections of METH (4 mg/kg). The increase in the TH mRNA level in the VTA was prevented by concurrent pretreatment with the NMDA receptor antagonist MK-801 (0.1mg/kg), suggesting the involvement of glutamatergic transmission in METH-induced alterations of tyrosine hydroxylase mRNA levels.;Progressive treatment with METH (4 mg/kg) elevated PPT mRNA levels in the dCPu and the NAc between days 1 and 6 of treatment; however, PPT mRNA levels returned to control values 15 days after cessation of treatment. Coadministration of the NMDA receptor antagonist MK-801 attenuated the elevation of PPT mRNA observed after chronic treatment with METH for 6 consecutive days. In contrast, PPE mRNA levels were significantly affected by acute treatment of METH and decayed by day 6. It is likely that the tachykinin peptides may not subserve a neuroadaptive role sustaining enduring sensitization to amphetamine, but play a role in the progressive augmentation of locomotor activity elicited by this class of drug.;Acute injection of METH (1 mg/kg) and cocaine (10 mg/kg) resulted in an elevation of dopamine efflux in all the regions measured. A METH challenge injection after 4 days withdrawal following 7 daily injections produced an even greater increase in dopamine release in the dCPu and long-lasting dopamine release in the NAc. Whereas, a cocaine challenge caused decreases and no significant changes in dopamine release in the dCPu and the NAc, respectively. In the somatodendritic regions, METH and cocaine challenges tend to decrease dopamine release compared with those induced by acute injections. Our results suggest that behavioral sensitization can be sustained during early withdrawal in the absence of augmentation in dopamine release in response to psychostimulant challenge.;Acute injection of METH (1 mg/kg) and cocaine (10 mg/kg) did not change glutamate efflux significantly in the neostriatum. Cocaine challenge increased glutamate release in both the dCPu and the NAc. In contrast, METH challenge increased glutamate release in the dCPu, but decreased glutamate efflux in the NAc. In the VTA and the SNc, acute METH decreased glutamate efflux whereas acute cocaine increased glutamate release. Challenge injections of METH and cocaine tend to enhance glutamate release. These data indicate that the neurotransmitter glutamate may be involved in behavioral sensitization to psychomotorstimulants.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
