Ethanol effects on brain concentrations of amitriptyline and the relationship to psychomotor function

The effect of amitriptyline (AMI), ethanol (ETOH), and ETOH followed by AMI on both general activity (open field) and motor performance (two rotorod tasks) was tested in reference to a saline-injected control. The combination (ETOH plus AMI) produced greater impairment on all three taks than did either drug alone. ETOH pretreatment also produced a 223% increase in the total tricyclic antidepressant (TCA) brain concentration. The decrement in motor performance was logarithmically related to total TCA brain concentrations in both animals treated with AMI alone and those pretreated with ETOH prior to AMI. The concentration which consistently produced behavioral impairment was similar to those previously reported to cause cognitive and electroencephalographic dysfunction in humans.