Effects of various psychotomimetic agents on the eeg and acetylcholine release from the cerebral cortex of brainstem transected cats

Abstract

The effects of i.v. administration of [Delta]9 THC, phencyclidine, the pyrrolidyl and piperidyl isomers of Ditran, and LSD-25 were determined on the spontaneous neocortical EEG and release of acetylcholine (ACh) from the somatosensory cortex of brainstem transected cats. [Delta]9 THC was given in doses of 0.5-11mg/kgi.v. to animals with a pretrigeminal midpontine transection. [Delta]9 THC produced neocortical high voltage EEG slow waves which were more prominent in the frontal areas of the brain. At the same time, arterial blood pressure and heart rate were reduced slightly. These effects were observable in doses of 0.5 mg/kg, but were more obvious at larger doses. The administration of amphetamine promptly antagonized the EEG changes induced by [Delta]9 THC. In doses of 0.5 mg/kg, [Delta]9 THC caused either no effect or a slight increase in the release of ACh from the cortex. Larger doses caused a progressive decrease in ACh release. The effects of [Delta]9 THC were antagonized by the administration of (+)-amphetamine in doses of 2.5 mg/kgi.v.Phencyclidine in doses of 1 mg/kg i.v. caused marked EEG changes consisting of high voltage, slow wave burst patterns, especially in the frontal cortex. At this dose, a slight increase in the cortical release of ACh was observed. Larger doses of 5 mg/kg which caused pronounced EEG changes did not significantly depress ACh release in contrast to pentobarbital (20 mg/kg) which dramatically reduced ACh release.Both isomers of Ditran caused EEG slowing in doses of 1mg/kg and a dramatic increase in the release of ACh from the cortex. They produced about a 200% increase in ACh release. In contrast, LSD-25 had no marked effect on ACh release. The effects were much less obvious and depended upon basal release levels. If basal release was low to moderate, LSD-25 in doses of 0.1 mg/kg slightly increased ACh release, while larger doses caused no greater increase. If baseline release of ACh was high, the drug decreased release slightly. In such pretrigeminal midpontine transected cats, LSD-25 usually caused EEG high voltage, slow waves, and a decrease in arterial blood pressure.It is concluded that various hallucinogens differentially affect the neocortical release of ACh in pretrigeminal midpontine transected cats. [Delta]9 THC caused a definite decrease in ACh release similar to anesthetic agents like pentobarbital. A dissociative anesthetic such as phencyclidine produced negligible effects. The isomers of Ditran caused a marked increased release of ACh while LSD-25 had negligible effects. Gross EEG neocortical changes were not directly correlated with the cortical release of ACh per se.