Abstract

The interaction of adrenergic blocking drugs and dl-amphetamine was studied quantitatively on the EEG of conscious, unrestrained, non-curarized rabbits with permanent electrodes implanted in the skull, by using the Drohocki Integrator of voltage output.

In rabbits depressed with pentobarbital (6 mg/kg), the injection of amphetamine (0.5 to 1.0 mg/kg) immediately returned the EEG pattern to control levels. This reversal was only partial with 0.25 mg/kg of amphetamine.

The analeptic effect of amphetamine was significantly inhibited by phenoxybenzamine (1.0 to 2.0 mg/kg), chlorpromazine (1.0 to 2.0 mg/kg), and Dibenamine (10 to 20 mg/kg). It was not significantly changed by azapetine (5 to 10 mg/kg), phentolamine (5 mg/kg) or dihydroergotamine (0.25 to 0.5 mg/kg).

The analeptic effect of caffeine and pentylenetetrazol was not blocked with doses of phenoxybenzamine which suppressed equivalent effects of amphetamine and methylphenidate.

Phenoxybenzamine, chlorpromazine and, to a smaller extent, Dibenamine, produced an EEG pattern of depression when injected alone. The other alpha-blocking agents used did not produce any significant change in the EEG when injected alone.

Dichloroisoproterenol (DCI) had a stimulant effect on the EEG and, in doses of 4 mg/kg, reversed almost completely the depressant action of pentobarbital. Smaller doses of DCI (1.0 to 2.0 mg/kg) which produced only a partial reversal of pentobarbital action, significantly increased the analeptic effect of amphetamine. This effect of DCI was blocked with proper doses of phenoxybenzamine. DCI also reversed partially the EEG depressant pattern produced by reserpine.

These results are discussed in terms of possible central adrenergic mechanisms.