Dose- and Time-Dependent Action of Morphine, Tramadol and Flupirtine as Studied by Radioelectroencephalography in the Freely Behaving Rat

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Abstract
The necessity of testing psychoactive drugs in awake freely moving animals has led to the development of a telemetry-based system which enables the pharmacologist to follow centrally active molecules in their time- and dose-dependent effects on electric brain activity in terms of changes in spectral power density of extracellularly recorded field potentials (tele-EEG). This report describes the effect of three analgesics with respect to bioelectric changes in frontal cortex, thalamus, striatum and reticular formation. Two opiate drugs, morphine and tramadol, behaved very similarly despite a tenfold difference in dosage, whereas flupirtine, a nonopiate analgesic, changed the frequency content of the EEG signals in an entirely different manner. The frequency pattern produced by the opiates closely resembles that of centrally acting serotonin uptake inhibitors and thus is consistent with the view of a serotonergic prevalence of neurochemical interactions within the recorded brain areas. In contrast, the action of flupirtine obviously can be attributed to a clonidine-like effect on noradrenergic alpha2-receptors. The results are discussed with respect to already known influences of these drugs on indoleaminergic and catecholaminergic transmission.