Dopamine-mediated increases in nigral substance P-like immunoreactivity.
The results reported herein strongly suggest that increased dopaminergic and not increased serotonergic activity is responsible for methamphetamine-induced increases in the nigral concentration of substance P-like immunoreactivity (SPLI). Thus, treatment of rats with the specific dopamine (DA) uptake blockers amfonelic acid (AFA) and nomifensine caused elevations in the SPLI levels within the substantia nigra similar to that of methamphetamine (METH). In contrast, the specific serotonin uptake blockers citalopram and chlorimipramine were without significant effects on this substance P (SP) system. Additional studies revealed that the mechanisms whereby the DA uptake blockers and METH influence the striatonigral SP pathway are likely different. Specifically, AFA, unlike METH, altered the SP system without causing changes in the monoaminergic synthesizing enzymes tyrosine and tryptophan hydroxylase; in addition, pretreatment with reserpine abolished the AFA effect on nigral SPLI but did not interfere with METH-mediated changes in the SP system.
Ritter
J K
JK
Schmidt
C J
CJ
Gibb
J W
JW
Hanson
G R
GR
D000818:Animals; D015283:Citalopram; D002997:Clomipramine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009268:Nalidixic Acid / Q000031:analogs & derivatives; D009287:Naphthyridines / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology; D013373:Substance P / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism*
D009287:Naphthyridines; D011437:Propylamines; D015283:Citalopram; D009627:Nomifensine; D012701:Serotonin; D013373:Substance P; D009268:Nalidixic Acid; D008694:Methamphetamine; D012110:Reserpine; D002997:Clomipramine; C006486:amfonelic acid; D004298:Dopamine