Role of glutamate ionotropic receptors in the dorsomedial hypothalamic nucleus on anxiety and locomotor behavior.
The medial hypothalamus is proposed to play an important role in the modulation of defensive responses. Administration of a NMDA receptor antagonist (AP7) into the dorsomedial hypothalamic nucleus (DMH) of rats reduced exploratory behavior in the open field and elevated plus-maze (EPM), but failed to produce anxiolytic effects in the latter test. The objectives of the present work were to test the hypotheses that (i) AP7 injections into the DMH would also fail to induce anxiolytic effects in another model of anxiety, the Vogel's punished licking test; (ii) injection into the DMH of other glutamate ionotropic antagonists would also decreased exploratory behavior; and (iii) the decrease in exploratory activity found after AP7 administration into the DMH does not involve any gross locomotor impairment. Male Wistar rats (n=5-16/group) with cannulas aimed at the DMH were submitted to the following behavioral tests: EPM, Vogel, catalepsy and rota-rod. Diazepam (3 mg/kg) and haloperidol (2.5 mg/kg) were used as positive controls in the Vogel, rota-rod and catalepsy tests. AP7 failed to modify the number of punished licks in the Vogel test. It also did not induce any change on the rota-rod and catalepsy tests. Diazepam increased the number of punished licks and reduced the latency to fall in the rota-rod. Both 7-chlorokynurenic acid (4-8 nmol), an antagonist of the glycine competitive site in the NMDA receptor and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo-[f]-quinoxaline-7-sulphonamide (NBQX, 1-10 nmol), a non-NMDA receptor antagonist, decreased the total distance moved in the EPM. The former compound also decreased open arm exploration at the dose of 4 nmol. The results suggest that the antagonism of ionotropic glutamate receptors in the DMH does not induce anxiolytic effects in the EPM or Vogel tests, but decreases exploratory behavior in a new environment.
Jardim
M C
MC
Dept. Pharmacology, School of Medicine, University of São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, SP, 14049-900, Brazil.
Guimarães
F S
FS
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000523:psychology*; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000502:physiology*
D011810:Quinoxalines; D017470:Receptors, Glutamate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid