Pharmacological studies of spinal cord adrenergic and cholinergic mechanisms and their relation to physical dependence on morphine.

Abstract

Several investigators (M~YzeE~ and KLI~G)~, 1962; Gu~-~TE~ 1963; SLoA~ et al., 1963) have demonstrated that chronic intoxication with morphine causes an increase in both brain and adrenal catecholamine levels. In addition, abrupt withdrawal of morphine in chronically intoxicated animals results in a fall in brain levels and increased excretion of" cateeholamines. These findings have suggested that there may be adaptive changes in cateeholamine metabolism during addiction to morphine, as well as increased utilization of catecholamines both in the brain and in the adrenal medulla during withdrawal. Because the spinal cord reflexes seem to be more amenable to physiological and pharmacological analysis than more complex supraspinal functional systems, and because both the effects of morphine and morphine dependence on spinal cord reflexes have been characterized (WmLEa and FRANK, 1948), it was felt that the importance and the necessity of adrenergic synapses and cateeholamines in the functioning of the spinal cord and in the genesis of physical dependence could be definitively assessed in this preparation. Because of possible interactions between eholinergie and adrenergic neurones in the central nervous system, pharmacological experiments were a]so conducted to assess the role of atropine sensitive mechanisms and presumably eholinergie synapses in the genesis of physical dependence. To these ends, three different series of experiments were conducted: (1) A study of the effects of peripherally active adrenergie and adrenergic-blocking agents on spinal cord reflexes in chronic spinal dogs, (2) a study of the effects of peripherally and centrally active cholinergie and cholinergic-blocking drugs in chronic spinal dogs, and