Male rats treated with reserpine were motionless and ingested only a f
ew of ten consecutive intraoral injections of a 1 M solution of sucros
e. While injection of apomorphine, a dopamine agonist, stimulated loco
motion and stereotyped sniffing in reserpinized rats, it did not react
ivate ingestive responses. The non-competitive N-methyl-D-aspartate re
ceptor antagonist MK801, however, stimulated locomotion as well as ing
estion suggesting involvement of glutamate in the suppressive effect o
f resperpine on ingestive responses. A series of experiments was there
fore undertaken to investigate the possible physiological role of glut
amate in feeding. For this purpose, we used Grill's intraoral intake t
est, in which the rat is infused intraorally with a sucrose solution a
nd the amount ingested measured. In untreated rats, MK801 dose-depende
ntly facilitated ingestion of the sucrose solution and antagonized inh
ibition of ingestion by cholecystokinin octapeptide. Administration of
cholecystokinin octapeptide or ingestion of sucrose increased the con
centration of glutamate in the nucleus of the solitary tract, a brain
stem relay transmitting sensory information from the gastrointestinal
tract to the forebrain. MK801 was found to bind specifically to this b
rain area and block the elevation of glutamate and dopamine levels whi
ch occurred after treatment with cholecystokinin octapeptide in this n
eural site. Together these data suggest that dopamine and glutamate ma
y interact within the nucleus of the solitary tract in controlling ing
estive behaviour.