Defensive reactions are counteracted by midazolam and muscimol and elicited by activation of glutamate receptors in the inferior colliculus of rats |
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Authors: | J E Pandossio M L Brandão |
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Institution: | (1) Laboratorio de Psicobiologia, Dept. de Psicologia, FFCLRP-USP, Campus, Av Bandeirantes 3900, 14049-901 Ribeir˜ao Preto, Brasil, IR |
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Abstract: | The inferior colliculus is involved in conveying auditory information of an aversive nature to higher cortical structures.
Gradual increases in the electrical stimulation of this structure produce progressive aversive responses from vigilance, through
freezing, until escape. Recently, we have shown that microinjections of NMDA into the inferior colliculus mimic these aversive
effects and that the neural substrates responsible for learned escape behavior in the inferior colliculus are regulated by
GABA−benzodiazepine mechanisms. In the present study, we extend these observations showing that unlearned aversive responses
are also depressed by muscimol and midazolam, both GABA-benzodiazepine agonists, and that microinjection of glutamate, an
excitatory amino acid, into the inferior colliculus can trigger freezing responses. Electrical stimulation of the inferior
colliculus of rats placed inside an open field allowed the determination of thresholds for the aversive responses, alertness,
freezing and escape. Systemic administration (3 and 5.6 mg/kg) as well as microinjections into the inferior colliculus of
the anxiolytic compound midazolam (10, 20 and 40 nmol) caused increases in threshold for these aversive responses. Similar
results were obtained following microinjections of the GABA-A agonist muscimol (0.1, 1 and 5 nmol) into this brainstem structure.
Microinjections of low doses of glutamate (5 nmol), presumed to activate mainly AMPA/kainate receptors, into the ventrolateral
division of the central nucleus of the inferior colliculus of rats placed inside a circular arena induced aversive reactions,
characterized by freezing responses. However, higher doses of glutamate caused no apparent effects. GDEE, an AMPA/kainate
receptor antagonist, inhibited, whereas AP7, a NMDA receptor antagonist, did not influence these responses. It is suggested
that GABA-benzodiazepine processes modulate the expression of defensive reactions in the inferior colliculus and that activation
of fast-acting excitatory amino acid receptors in this midbrain region can trigger the initial steps of the defense reaction
without eliciting the motor explosive behavior usually seen following the activation of NMDA receptors.
Received: 13 May 1998 / Final version: 12 August 1998 |
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Keywords: | Inferior colliculus Aversion Glutamate Muscimol Midazolam |
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