The effect of 4 wk of streptozocin (STZ)-induced diabetes on the transmission time of the auditory-evoked brain stem response (ABR) was examined in conscious male Sprague-Dawley rats. Distal nerve transmission time of the auditory pathway (latency of peak II), which includes conduction along the 8th cranial nerve, increased in diabetic rats (n = 9) relative to nondiabetic rats (n = 17). The difference in peak II latency between diabetic and control rats was significant beginning 2 wk after the induction of diabetes (P less than .05). In contrast, 4 wk of STZ-induced diabetes had no effect on the central transmission time of the auditory pathway (interpeak latency between peaks II and IV). Oral administration of tolrestat, a structurally novel aldose reductase inhibitor (n = 8; 20 mg/kg twice daily 1 wk before and 4 wk after STZ injection), prevented the diabetes-induced increase in distal nerve transmission time. These findings indicate that experimentally induced diabetes can result in a nerve dysfunction as measured by the increased latencies of the early components of the ABR. Furthermore, because tolrestat prevents these changes in the ABR, aldose reductase and the polyol pathway are implicated in this neuropathy.

The purpose of this study was to extend our previous work with the auditory-evoked brainstem response and determine whether galactosemia would produce a functional neuropathy similar to that previously seen in streptozocin-induced diabetic rats. Sprague-Dawley male rats implanted with cortical electrodes received either normal chow (n = 17) or a 50% galactose diet (n = 17) for 5 weeks. Peak II latency of the auditory-evoked brainstem response, interpreted as a functional measure of the auditory nerve (VIII cranial) in rats, was significantly prolonged in galactose-fed rats relative to controls (P less than 0.05). These results demonstrate a functional deficit in the auditory nerves of galactosemic rats. The deficit in the auditory-evoked brainstem response of galactosemic rats is similar to our previous finding in streptozocin-induced diabetic rats.

Notvest, R.R., T.A. Emrey, and J.J. Inserra: Effect of vinpocetine on age-related differences in brain function of aged Fischer rats. Drug Dev. Res. 14:325-333, 1988. Vinpocetine, an eburnamenine derivative, is under clinical investigation as a cerebral activator for use in Alzheimer's and other diseases characterized by symptomatic cognitive and attentional deficits. In this study, vinpocetine was evaluated by examining its effect on the electrocorticogram (ECoG) of aged (26-month-old) Fischer-344 rats. Significant age-related differences were apparent for all ECoG parameters examined, suggesting a cerebral deficit in aged rats. Vinpocetine, administered orally (p.0.) over the dose range of 0.3 to 30 mgikglday p.0. for 5 days, diminished the age-related differences in the ECoG. These findings provide evidence that vinpocetine may serve as a useful therapeutic agent in diseases characterized by cerebral deficits.