AMPA, kainic acid, and N-methyl-D-aspartic acid stimulate locomotor activity after injection into the substantia innominata/lateral preoptic area.
The substantia innominata/lateral preoptic area (SI/LPO) is a subpallidal region which has been shown to regulate the hypermotility produced by drugs acting in the nucleus accumbens. Evidence has been presented that the SI/LPO contains glutamatergic nerve terminals and receptors for excitatory amino acids. The purpose of this study was to determine the effects of the activation of excitatory amino acid receptors in the SI/LPO on locomotor activity following the direct injection of excitatory amino acids into this brain site. It was found that the bilateral injection of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA), kainic acid, and N-methyl-D-aspartic acid into the SI/LPO produced marked dose-dependent stimulations of locomotor activity which resembled the effects of these agents after their injection into the nucleus accumbens. The effect, however, was bell-shaped in that at high doses, the locomotor activity values decreased from their peak values. The coinjection of gamma-glutamylaminomethylsulfonate (GAMS) with AMPA into the SI/LPO was found to inhibit the hypermotility response to AMPA at doses that were unable to produce a significant inhibition of the hypermotility responses to kainic acid or N-methyl-D-aspartic acid. The injection of 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the SI/LPO inhibited the hypermotility responses to AMPA or kainic acid while having no significant inhibitory effect on N-methyl-D-aspartic acid stimulated locomotor activity. The injection of D-alpha-aminoadipic acid into the SI/LPO produced a significant inhibition of the hypermotility response produced by N-methyl-D-aspartic acid at a dose that did not produce a significant inhibition of the hypermotility response produced by AMPA.(ABSTRACT TRUNCATED AT 250 WORDS)
Shreve
P E
PE
Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus 43210.
Uretsky
N J
NJ
D015074:2-Aminoadipic Acid / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001479:Basal Ganglia / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005973:Glutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D007051:Ibotenic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate; D010080:Oxazoles / Q000494:pharmacology*; D011301:Preoptic Area / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013377:Substantia Innominata / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D010080:Oxazoles; D011810:Quinoxalines; D005973:Glutamine; D015074:2-Aminoadipic Acid; D007051:Ibotenic Acid; D001224:Aspartic Acid; C056723:FG 9041; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C042626:gamma-glutamylaminomethylsulfonic acid; D007608:Kainic Acid