GABA and glutamate interact in the substantia innominata/lateral preoptic area to modulate locomotor activity.
Previous studies have shown that excitatory amino acid agonists or GABAergic antagonists injected into the substantia innominata/lateral preoptic area (SI/LPO) can produce the stimulation of coordinated locomotor activity. The purpose of the present study was to determine whether GABAergic and glutamatergic mechanisms in the SI/LPO interact to regulate locomotor activity. The stimulation of locomotor activity produced by the bilateral injection into the SI/LPO of 0.5 microgram of AMPA, a potent quisqualic acid receptor agonist, was antagonized by the coinjection of muscimol (25 ng). Similarly, the stimulation of locomotor activity produced by picrotoxin, an inhibitor of the effects of GABA, was antagonized by the coinjection of DNQX, which has been shown to inhibit the behavioral effects of both kainic acid and quisqualic acid, or a high dose of GAMS (25 micrograms), which has been shown to inhibit the behavioral effects of both AMPA and N-methyl-D-aspartic acid. In contrast, a lower dose of GAMS (5 micrograms), which selectively inhibited the locomotor stimulation produced by AMPA, or D-alpha-aminoadipic acid, at a dose (10 micrograms) which selectively inhibited the locomotor stimulation produced by N-methyl-D-aspartic acid, did not inhibit the effects of picrotoxin. However, the combination of both GAMS (5 micrograms) and D-alpha-aminoadipic acid (10 micrograms) produced a marked inhibition of the response to picrotoxin. These results suggest that the hypermotility response elicited by picrotoxin can only be antagonized when more than one subtype of excitatory amino acid receptor is antagonized and support the concept that excitatory amino acid receptors and GABAergic receptors in the SI/LPO interact to regulate locomotor activity.
University of Nebraska Medical Center, Department of Pharmacology, Omaha 68198-6260.
P E
PE
Shreve
N J
NJ
Uretsky
D015074:2-Aminoadipic Acid / Q000494:pharmacology; D000818:Animals; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D005973:Glutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009118:Muscimol / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011301:Preoptic Area / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D015074:2-Aminoadipic Acid; D005971:Glutamates; D018698:Glutamic Acid; D005973:Glutamine; D007051:Ibotenic Acid; D009118:Muscimol; D016202:N-Methylaspartate; D010852:Picrotoxin; D011810:Quinoxalines; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D005680:gamma-Aminobutyric Acid; C056723:FG 9041; C042626:gamma-glutamylaminomethylsulfonic acid