DEVELOPMENT AND USE OF PHARMACOLOGICAL PROBES OF THE CNS IN MAN - EVIDENCE OF CHOLINERGIC ABNORMALITY IN PRIMARY AFFECTIVE-ILLNESS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 15  (6) , 925-955
Abstract
The role of cholinergic mechanisms in the regulation of CNS functions was studied in normal humans. In vivo pharmacological techniques were developed to assess central neurotransmitter activity in normals and apply them in primary affective illness and other neuropsychiatric conditions. Central cholinergic stimulation by cholinomimetics induced rapid eye movement (REM) sleep, dreaming, cortical arousal and accelerated the REM cycle. Effects on memory included enhancement of serial learning, short-term consolidation of low-imagery words and retrieval of clustered information. Analgesia and reduction of the P100 component of visual EEG evoked responses were noted after physostigmine. Using the induction of REM sleep by arecoline as a marker of central cholinergic functioning, it was possible to demonstrate the phenomenon of pharmacological denervation supersensitivity in normal humans after pretreatment with scopolamine and demonstrate a significantly faster REM induction by arecoline in 2 groups of patients with primary affective illness (remitted and depressed) compared to normals. Rapid REM induction was found, not only in remitted patients who were drug-free for 2 wk but in patients who had never received somatic therapy. Pretreatment with scopolamine on 3 consecutive mornings induced sleep changes at night in normals similar to several sleep abnormalities reported in primary affective illness. This was confirmed by a multivariate discriminate analysis program, which had previously separated depressed patients, insomniacs and normals. It is proposed that cholinergic abnormalities may be present in primary affective illness during the ill and the well states.