GABAergic and glutamatergic modulation of exploratory behavior in the dorsomedial hypothalamus.
Systemic injection of glutamate NMDA receptor antagonists or drugs that facilitate GABA(A)-mediated neurotransmission produces anxiolytic effects. The dorsomedial hypothalamic (DMH) region is proposed to be a possible site of action of these drugs. The objective of the present study was to investigate if facilitation of GABA(A)-mediated neurotransmission or blockade of NMDA receptors in the DMH would produce anxiolytic effects in the elevated plus-maze (EPM). Seven days after surgery, male Wistar rats with unilateral cannulas in the DMH were submitted to the behavioral studies. Results showed that midazolam, a benzodiazepine anxiolytic (30-60 nmol/0.3 microl), produced a dose-dependent increase in open arm exploration without changing the number of enclosed arm entries, indicating an anxiolytic effect. This effect was antagonized by previous treatment with flumazenil, a benzodiazepine receptor antagonist (60 nmol/0.3 microl). Flumazenil alone had an anxiogenic effect, decreasing exploration of the open arms of the EPM. 2-Amino-7-phosphonoheptanoic acid (AP7), an NMDA receptor antagonist (0.2-2 nmol/0.3 microl), did not modify open arm exploration but decreased general exploratory activity. These results indicate that benzodiazepine receptors located in the DMH could modulate anxiety. Interference with NMDA receptor-mediated neurotransmission in this region, however, seems to change general exploratory activity rather than anxiety.
Jardim
M C
MC
Department of Pharmacology, FMRP, Campus USP, Ribeirão Preto, SP 14049-900, Brazil.
Guimarães
F S
FS
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D005442:Flumazenil; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid; D008874:Midazolam