GABAergic Modulation of Inferior Colliculus Excitability: Role in the Ethanol Withdrawal Audiogenic Seizures

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GABAergic Modulation of Inferior Colliculus Excitability: Role in the Ethanol Withdrawal Audiogenic Seizures

Post by Amanita Research » Tue Oct 01, 2019 8:56 pm

https://www.ncbi.nlm.nih.gov/pmc/articl ... d3ipC1iixI

Abstract: The role of the inferior colliculus and GABAeric transmission within this structure in the development of susceptibility to sound-induced seizures in ethanol-dependent rats was examined. Ethanol-dependent rats with bilateral electrolytic lesions which destroyed approximately 50.0 ± 6.4% of the inferior colliculus failed to exhibit susceptibility to sound-induced seizures. However, comparable medial geniculate body lesions (82.7 ± 2.7% complete) did not alter wild running, slightly reduced tonus and actually increased clonus susceptibility in rats treated similarly with ethanol. As reported previously, bilateral injection of either muscimol (43–263 pmol/site) or racemic baclofen (520–1580 pmol/site) into the inferior colliculus also suppressed seizure susceptibility. Other studies in ethanol-naive animals found that bilateral microinfusion of(+)-bicuculline methoiodide (2 or 20 pmol/min for up to 5 min) into the inferior colliculus induced wild running and clonus closely resembling sound-induced seizure responses in ethanol-dependent rats. Although similar microinjections of (+)-bicuculline methiodide (0.4 pmol/min for 5 min) into the inferior colliculus did not induce seizure activity directly, an increased susceptibility to sound-induced seizures was observed. Electrolytic lesions of the medial geniculate body did not block wild running responses induced by (+)-bicuculline methiodide, but slightly reduced clonus. Five-minute infusions of picrotoxin (200 pmol/min), Ro5-3663 (2000 pmol/min), kainic acid (20 or 200 pmol/min), strychnine (2000 pmol/min) or carbachol 2000 pmol/min) into the inferior colliculus of ethanol-naive rats all induced bicuculline-like seizures. Seizures induced by bicuculline methiodide, picrotoxin or Ro5-3663 occurred within 5 min after the start of infusions. Seizures induced by non-GABAergic drugs were delayed 10 to 15 min after beginning the infusions. Finally, muscimol (263 pmol/site) administered into the inferior colliculus blocked sound-induced seizures in Uaz:AGS (S.D.) epilepsy prone rats and prevented seizures induced by bicuculline or kainic acid infused into this brain site. However, seizure responses after i.v. bicuculline infusion or maximal electroshock were not diminished by injection of this dose of muscimol into the inferior colliculus. These results suggest that adaptation in GABAergic inhibitory mechanisms in the inferior colliculus could play an important role in the genesis of sound-induced seizures in ethanol-dependent rats, although additional mechanisms involving excitatory processes may also be important.

The inferior colliculus is a prominent relay nucleus in the auditory pathway and appears to play an important role in modulating auditory sensory input to the cerebral cortex (Morest, 1975). Recent experimental evidence also suggests that the inferior colliculus is involved in the generation of sound-induced seizures. For example, destruction of the inferior colliculus (Kesner, 1966; Wada et al., 1970; Ward, 1971; Henry et al., 1972) prevents audiogenic seizures in sound-sensitive rats and mice. This action does not appear to be due to interuption of sensory input to the cerebral cortex because lesions of other relay nuclei such as the medial geniculate body, nucleus of the lateral lemniscus, superior olivary complex or ventral cochlear nucleus all fail to block audiogenic seizures (Koenig, 1957; Duplisse et al., 1974; Willott & Su, 1980).

GABAergic neurotransmission in the inferior colliculus may play an important role in modulating susceptibility to sound-induced seizures. Duplisse et al. (1974) have shown that microinjection of GABA into the inferior colliculus can prevent seizures in rats genetically susceptible to audiogenic seizures. GABAergic transmission in the inferior colliculus may also play an important role in the modulation of audiogenic seizure susceptibility in ethanol-dependent rats. Microinjection of GABA agonists, such as muscimol (263 pmol/site), into the inferior colliculus blocks completely sound-induced seizures during ethanol withdrawal (Frye et al., 1983). As yet, it is unclear whether the inferior colliculus plays an active role in initiation of genetic or ethanol withdrawal-induced audiogenic seizures. However, the inferior colliculus of ethanol-naive rats does appear to be uniquely sensitive to bicuculline, a GABA antagonist, that can evoke audiogenic seizure-like responses when infused there in exceedingly small amounts (Duplisse et al., 1974; Frye et al., 1983). In addition, a single electrical stimulation of the inferior colliculus with relatively small currents can evoke seizure responses resembling audiogenic seizures (McCown et al., 1984), suggesting that this brain area may be important in initiating the audiogenic seizure response. The present studies were designed to evaluate further the role of the inferior colliculus in the development of susceptibility to audiogenic seizures in the ethanol-dependent rat, and to characterize the relative sensitivity of the inferior colliculus to a variety of pharmacologically distinct chemical excitants.

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