Suppression of serotonin-dependent cerebral activation: a possible mechanism of action of some psychotomimetic drugs.

Rats treated with centrally acting anti-muscarinic (atropinic) drugs display large amplitude irregular slow waves in both the neocortex and hippocampus during behavioral immobility and some stereotyped automatic behaviors (Type 2 behavior). However, rhythmical slow activity (RSA) in the hippocampus and low voltage fast activity (LVFA) in the neocortex occur in close correlation with spontaneous changes in posture, head movement, walking, rearing, swimming or struggling when held (Type 1 behavior). Previous research has indicated that such atropine-resistant RSA and LVFA is dependent on brain serotonin. In the experiments reported here, atropinized rats were given a test drug or a control injection while hippocampal and neocortical activity and behavior were recorded. Several psychotomimetic drugs (phencyclidine; (d,l)-N-allyl-N-normetazocine (SKF-10,047); d,l-cyclazocine; and N-ethyl-1-phenyl-cyclohexylamine) strongly suppressed atropine-resistant RSA and LVFA in doses that were compatible with active behavior. Ketamine had a weak effect but a variety of other drugs were inactive in this test. It is suggested that the psychotomimetic effect of phencyclidine and the psychotomimetic opioids is due, at least in part, to suppression of serotonin-dependent activation of the cerebral cortex.