There is a paucity of information available relating to the manner in which drugs of abuse affect those neurophysiological systems that subserve sensory input. Four agents that alter sensory input and levels of consciousness (THC, mescaline, LSD and morphine) were selected as test agents for these studies. We propose to test the hypothesis that phenomena such as hallucinations and synesthesia are principally elaborated at the cortical level in those cortical projection sites that have been identified as secondary or polysensory. Disruption of complex sensory function at these sites could result from alterations of the multiple modality specific projections that converge here, or could be a result of altered modulation of modality specific and polysensory input by subcortical systems, specifically, the reticular and limbic complex. These studies will determine whether altered sensory input at primary and polysensory cortical sites can be correlated to the hallucinogenic potential of abused drugs. Anesthetized acute, immobilized, and chronically implanted, unrestrained cats will be used for these studies. In order to simulate the normal environmental situation, we will study the effect of the test agents on the cortical responses elicited by simultaneous or temporarily coupled activation of multiple sensory modalities. Field potentials will be analyzed to characterize any alteration in sensory input. The contribution of cholinergic mechanisms to the elaboration of sensory responses as well as to the alteration of these responses by the test drugs will be evaluated by using selected cholinergic agonists and antagonists. We will also determine whether cholinergic mechanisms play a role in the modulation of sensory input by the reticular or limbic system. These studies may provide an animal model which would effectively predict the hallucinogenic potential of new chemical agents.