Effect of Alcohol on Hypothalamus Neurons

Alcohol (EtOH) is the most frequently consumed legal drug that causes addiction and severe diseases. Furthermore, alcoholism is a main comorbidity in patients suffering from another psychiatric disorder. The best known cellular mechanism of EtOH is the enhancement of GABA action on the GABA-A receptor, hence increasing the chloride ion influx, hyperpolarizing the membrane potential and reducing the neuronal firing rate (FR). In extracellular recordings from temperature sensitive neurons in hypothalamic rat brain slices at 37°C we have seen that application of 0.1% to 0.4% EtOH lead to a triphasic response: the FR drastically increased (phase 1), strongly declined immediately (phase 2), and finally recovered under ongoing EtOH application to a FR higher than before application (phase 3). During ongoing sinusoidal temperature changes ranging from 35°C to 39°C application of EtOH lead to a sensitization of warm sensitivity: a stronger decrease of the FR at cooling and a stronger increase at warming was observed. Additional patch-clamp experiments in a murine hypothalamic neuronal cell line (GT1) showed that EtOH has intrinsic effects independent from GABA. Our data suggest that cellular mechanisms of acute alcohol application have strongly nonlinear effects with regard to different concentrations, application duration, and additional stimuli. Wollweber BT et al, J Thermal Biol 2004; 29: 345–350