The effect of methadone addiction on cyclic nucleotide levels in regions of rat brain.
Studies of tissue culture cells and tissue slices have implicated the nucleotides, cyclic AMP and cyclic GMP, in the mechanism of action of opiates. However, there are little in vivo data to corroborate this hypothesis. We addicted rats to the synthetic opiate, methadone, by providing the drug in their drinking water (dosage 2.1 mg./kg./day). The two cyclic nucleotides were measured in four brain areas which contain a high concentration of opiate receptors: amygdala, neostriatum, periventricular grey, and thalamus. Data were obtained after acute exposure of the drug (1 day), tolerance (35 days), withdrawal (35 days on drug then 1 day off drug), and readjustment (35 days on drug then 21 days off drug). Cyclic GMP levels were low (0.03 pmol./mg. tissue) in the four regions and did not differ significantly during the experiment. Cyclic AMP levels were higher (1-3 pmol./mg.) and fluctuated consistently in the four regions. After acute methadone treatment, there was a reduction in cyclic AMP, which continued at lower levels after tolerance. One day of withdrawal led to increased cAMP, which rose to near control levels. After readjustment, the levels were reduced. These data indicate an involvement of cyclic AMP in the addiction and withdrawal processes in the intact animal.
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D008297:Male; D008691:Methadone; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D019966:Substance-Related Disorders / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism; D014018:Tissue Distribution
D000242:Cyclic AMP; D006152:Cyclic GMP; D008691:Methadone