From Rats to Monkeys to Man—The Neurophysiology of Alcoholism: A Tribute to Henri Begleiter

HE SECOND ENTRY in Henri Begleiter’s extensive curriculum vitae was entitled ‘‘Changes in Auditory Evoked Responses Induced by Alcohol’’ (Gross et al., 1966). It signaled a 4-decade-long scientific career dedicated to the understanding of the actions of acute alcohol on the brain, the consequences of alcohol abuse and alcoholism, and the genetic determinants rendering individuals at risk to develop alcoholism. While his research took many and varied paths, he was at heart a neurophysiologist who sought to understand brain function by interrogating the electrical activity observable from probes inside the brain or noninvasively from electrodes outside the brain. Here I have selected a few of Henri’s neurophysiology-based publications to trace the development of his thinking about alcohol and the brain as it encompassed three species—rats, monkeys, and man. In his 1975 paper ‘‘Evoked Potential Changes During Ethanol Withdrawal in Rats’’ (Begleiter and Coltrera, 1975), a skull screw electrode over visual cortex and an implanted electrode in the ascending reticular function were used to record the EEG response to light flashes in Long Evans rats after alcoholization and subsequent withdrawal. The methodology in those days relied on the dedicated computer of average transients (the CAT), analog plotting of averaged evoked potentials on graph paper, and manual estimation of response amplitudes and latencies. The results indicated CNS hyperexcitability 24 hours after the last of several days of intragastric alcohol administration in the rat, consistent with human observations. Later (1977) with his career-long colleague Bernice Porjesz, persistence of this hyperactivity in the rat at least 5 weeks after withdrawal was demonstrated (Begleiter and Porjesz, 1977). Using a postwithdrawal alcohol challenge they observed progressive increase in brain electrical activity rather than the depression seen in control animals, consistent with a subacute postwithdrawal syndrome and with implication for mechanisms of craving. In 1980 Henri and his colleagues repeated the rat studies in Bonnet monkeys using implanted electrodes in several brain regions (Begleiter et al., 1980). The animals were made alcohol dependent with large intragastric doses (5.0 g/kg) daily with the animals reaching peak blood alcohol concentrations of 4300 mg%. As with the rat studies the monkeys were then challenged with alcohol (2.0 g/kg) 5 weeks after withdrawal. Using visual evoked potentials, persistent CNS hyperexcitability was reactivated with reexposure to alcohol. The pattern observed in the rat was demonstrated in the monkey. Henri was a pioneer in alcohol translational research