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Distinct responses of basal ganglia substance P systems to low and high doses of methamphetamine
Author(s) -
Hanson Glen R.,
Bush Lloyd,
Keefe Kristen A.,
Alburges Mario E.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01053.x
Subject(s) - methamphetamine , globus pallidus , basal ganglia , microdialysis , substantia nigra , dopaminergic , striatum , medicine , endocrinology , dopamine , substance p , extracellular , neuropeptide , neurotensin , chemistry , biology , pharmacology , receptor , central nervous system , biochemistry
Substance P (SP) is a neuropeptide closely associated with basal ganglia dopaminergic neurons. Because some neuropeptide systems in the basal ganglia (i.e. neurotensin and metenkephalin) are differentially affected by treatment with low or high doses of methamphetamine, we determined if basal ganglia SP pathways were also differentially influenced in a dose‐dependent manner by this psychostimulant. Employing in vivo microdialysis, it was observed that the lowdose (0.5 mg/kg) of methamphetamine increased the extracellular concentration of SP in the substantia nigra, but not in globus pallidus or striatum. In contrast, the high dose (10 mg/kg) of methamphetamine did not increase extracellular SP content in any of these structures. The effect of the low‐dose methamphetamine treatment on nigral extracellular SP levels was blocked by pre‐treatment with either a D 1 or D 2 antagonist. In addition, 12 h after similar methamphetamine treatments, a dose‐dependent differential response in SP tissue levels occurred in some of the regions examined. When these changes occurred, the low dose of methamphetamine usually reduced, whereas the high dose increased, SP tissue content. This study demonstrated opposite responses of the basal ganglia SP system to low and high doses of methamphetamine and suggested that a combination of dopamine D 1 and D 2 receptor activity contributed to these effects.