Transient increase in [ 3H]Ro 15–4513 specific binding in the superficial gray layer of the rat superior colliculus induced by visual deafferentation

Abstract

The imidazodiazepine compound [ 3H]Ro 15–4513, a partial inverse agonist of benzodiazepine recetors of the central type, binds with high affinity (order of 10 −8 M) to a single population of benzodiazepine binding sites in the mammalian central nervous system. A quantitative autoradiographic study was carried out to determine the effects of one eye removal on [ 3H]Ro 15–4513 specific binding to rat brain sections in the superficial gray layer or stratum griseum superficiale (SGS) of the superior colliculus. Retinal afferent degeneration due to right eye removal, performed 3 and 7 days before sacrifice, led to a significant and symmetrical increase in the [ 3H]Ro 15–4513 specific binding in both right and left SGS by enhancing the binding affinity of the radioligand. This transient phenomenon disappeared when a longer survival period of 45 days was allowed to elapse. Conversely, unilateral lesion of the primary visual areas has no apparent effects on the specific binding of the radioligand. The absence of any loss of binding sites after either type of lesion suggests that the benzodiazepine receptors are probably not situated on the optic nerve axon terminals, nor on the cortical axon terminals originating from primary visual areas. In the SGS, as in other rat brain structures, benzodiazepine receptors of the central type are functionally coupled with GABA A receptors and form ‘GABA A receptors/benzodiazepine receptors/chloride channel’ complexes. The involvement of the local GABAergic system in the postlesion plasticity of benzodiazepine receptors was studied by testing the effects of exogenously applied GABA on [ 3H]Ro 15–4513 specific binding. The amino acid had potent inhibitory effects both on the amount of specific binding in the control rat SGS and on the increased amount of binding induced in right and left SGS by retinal afferent degeneration. The induced increase in specific binding was blocked by the addition of 50 μM GABA in the incubation medium. These GABA inhibitory effects on specific binding of the radioligand were only weakly antagonized by 25 μM bicuculline, a GABA A antagonist. These results suggest that retinal deafferentation induced an increase in the affinity of the inverse agonist benzodiazepine binding sites, probably by decreasing GABA control on the retino-collicular neurotransmission.