Antiaversive action of benzodiazepines on escape behavior induced by electrical stimulation of the inferior colliculus.
In the present work, evidence is presented for the involvement of inferior colliculus in the generation and elaboration of aversive responses which suggests that this structure may be part of a brain system that commands aversive states. Electrical stimulation of the inferior colliculus of rats placed inside an open field allowed the determination of thresholds for the escape response. Afterward these rats were placed inside a shuttle box and submitted to a switch-off paradigm. Electrical stimulation of the inferior colliculus was applied at a current intensity 5% below the escape threshold. This electrical stimulation showed clear aversive properties: the rats quickly learned to interrupt it. Systemic administration (3 and 5.6 mg/kg) as well as inferior colliculus microinjections (10 and 20 nmol) of the anxiolytic compound midazolam caused dose-dependent increases in the latency and reductions in the frequency of switch-off responses to the inferior colliculus electrical stimulation. Similar results were obtained following microinjections into this brainstem structure of the GABA-A agonist muscimol (0.1 and 0.5 nmol). These results suggest that neural substrates commanding defensive behavior in the inferior colliculus may be depressed by benzodiazepines as part of the anxiolytic action of these compounds. This antiaversive action may be produced by the enhancement of GABA-A mechanisms.
Melo
L L
LL
Laboratório de Psicobiologia, Faculdade de Filosofia, Universidade de São Paulo, Brasil.
Cardoso
S H
SH
Brandão
M L
ML
D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology*; D007245:Inferior Colliculi / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D008874:Midazolam