title: Modulation of haloperidol-induced catalepsy in rats by GABAergic neural substrate in the inferior colliculus.
abstract: Not only is the inferior colliculus (IC) a highly important center of integration within the central auditory pathway, but it may also play a modulatory role in sensory-motor circuitry. Previous evidence from our laboratory relating the IC to motor behavior shows that glutamate-mediated mechanisms within the IC modulate haloperidol-induced catalepsy. The high density of GABAergic receptors in the IC led to this study of a possible link between these receptors, haloperidol-induced catalepsy, and a possible involvement of the blockade of dopaminergic receptors. Catalepsy was evaluated by positioning both forepaws of rats on an elevated horizontal wooden bar and recording the time that the animal maintained this position. The present study shows that haloperidol-induced catalepsy was enhanced by local microinjection into the IC of midazolam (20nmol/0.5μl), a benzodiazepine receptor agonist, whereas animals receiving a microinjection of bicuculline (40 or 80ng/0.5μl), a GABAergic antagonist, showed a reduction in the time of catalepsy. However, the microinjection of haloperidol (2.5 or 5.0μg/0.5μl) bilaterally into the IC did not induce catalepsy. Therefore, our results suggest the involvement of the IC in the modulation of catalepsy induced by haloperidol, even though the dopaminergic mechanisms of the IC are unable to induce catalepsy when blocked by the direct microinjection of haloperidol. It is thus possible that the IC plays a role in sensorimotor gating and that GABA-mediated mechanisms are involved.
authors.affiliation: Laboratório de Neuropsicofarmacologia, Universidade São Francisco, Avenida São Francisco de Assis, 218, Bragança Paulista, SP 12916-900, Brazil; Faculdade de Medicina de Itajubá, Avenida Renó Júnior, 368, São Vicente, Itajubá, MG 37502-138, Brazil.
authors.forename: J G
authors.initials: JG
authors.lastname: Tostes
authors.forename: P
authors.initials: P
authors.lastname: Medeiros
authors.forename: L
authors.initials: L
authors.lastname: Melo-Thomas
mesh_terms: D000818:Animals; D002375:Catalepsy / Q000139:chemically induced / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D007245:Inferior Colliculi / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018492:Dopamine Antagonists; D058787:GABA-A Receptor Antagonists; D005680:gamma-Aminobutyric Acid; D006220:Haloperidol
keywords: (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate; GABA; IC; MDZ; MK-801; N-methyl-d-aspartate; NMDA; PD; Parkinson’s disease; SNpr; bicuculline; catalepsy; haloperidol; inferior colliculus; midazolam; substantia nigra pars reticulata