[EXPERIMENTAL MODELS OF ALCOHOLIC NEUROPATHY IN RATS.]

The aim of this work was to study the behavioral and histopathomorphological signs of peripheral neuropathy development in male Wistar rats on the model of alcoholic neuropathy. Chronic consumption of ethanol solution with concentration increasing from 7.47 to 26.2% (w/w) resulted in neuropathy (allodynia) de- velopment after 8 weeks of chronic alcohol administration. The behavioral signs of allodynia became significant on the 8th week and were retained up to the end of experiment (15 weeks of ethanol administration). The reference drug gabapentin effectively reduced the manifestation of allodinia. Histological exami- nation of sciatic nerve preparations from animals killed after ethanol consumption for 5, 10 and 15 weeks revealed the development of histopathomorphological pattern with increasing duration of chronic alcoholization. At the initial stage, the morphological basis of observed behavioral manifestations was provided by excess lipid deposition in peri/epineurium of nerve specimens). The further increase in treatment duration (up to 10 and 15 weeks) was associated with demye- lination and development of inflammation of the sciatic nerve. This experimental model allows one to investigate the efficacy of new neuroprotective and ana- lgesic substances - potential drugs for both prevention and management of neuropathy.

Behavioral deficits and cellular damage following developmental ethanol exposure in rats are attenuated by CP-101,606, an NMDAR antagonist with unique NR2B specificity.

NMDAR-mediated excitotoxicity has been implicated in some of the impairments following fetal ethanol exposure. Previous studies suggest that both neuronal cell death and some of the behavioral deficits can be reduced by NMDAR antagonism during withdrawal, including antagonism of a subpopulation of receptors containing NR2B subunits. To further investigate NR2B involvement, we selected a compound, CP-101,606 (CP) which binds selectively to NR2B/2B stoichiometries, for both in vitro and in vivo analyses. For the in vitro study, hippocampal explants were exposed to ethanol for 10 days and then 24 h following removal of ethanol, cellular damage was quantified via propidium iodide fluorescence. In vitro ethanol withdrawal-associated neurotoxicity was prevented by CP (10 and 25 nM). In vivo ethanol exposure was administered on PNDs 1-7 with CP administered 21 h following cessation. Activity (PNDs 20-21), motor skills (PNDs 31-33), and maze navigation (PNDs 43-44) were all susceptible to ethanol insult; treatment with CP (15 mg/kg) rescued these deficits. Our findings show that CP-101,606, a drug that blocks the NR2B/2B receptor, can reduce some of the damaging effects of "3rd trimester" alcohol exposure in our rodent model. Further work is clearly warranted on the neuroprotective potential of this drug in the developing brain.