TY - JOUR
T1 - Changes in brain cyclic AMP metabolism and acetylcholine and dopamine during narcotic dependence and withdrawal
AU - Merali, Z.
AU - Singhal, R. L.
AU - Hrdina, P. D.
AU - Ling, G. M.
N1 - Funding Information:
This investigation was supported by the Non-Medical Uae of Druga Directorate of Health and Welfare Canada under its program of Research on Drug Abuse (RODA) and by grants from the Ontario Mental Health Foundation . The authors are grateful to Mr. S. Rlosevych, Director of Medical Communications and his staff for their skilled assistance in the preparation of illustration .
PY - 1975/6/15
Y1 - 1975/6/15
N2 - Effects of morphine administration were studied on cyclic AMP metabolism in several regions of rat brain. In the cortex, cerebellum and thalamus-hypothalamus, morphine dependence did not alter the activity of either adenylate cyclase or phosphodiesterase. However, during withdrawal from the opiate treatment, adenylate cyclase activity declined in all three regions studied. In contrast, the striatal cyclic AMP metabolism was enhanced during morphine treatment as reflected by elevated endogenous cyclic AMP and increased adenylate cyclase. Furthermore, narcotic dependence produced significant increases in acetylcholinesterase activity of rat striatum. Whereas morphine withdrawal reversed the changes in striatal acetylcholine levels and acetylcholinesterase activity, the enhanced striatal dopamine remained unaltered. Although the activity of striatal adenylate cyclase was significantly reduced when compared to the morphine-dependent rats, the drop in cyclic AMP levels was not significant. Methadone replacement did not affect the changes in striatal dopamine seen in morphine-withdrawn rats. Whereas dopamine stimulated equally well the striatal adenylate cyclase from control or morphine-dependent animals, it failed to stimulate the striatal enzyme from rats undergoing withdrawal. The crude synaptosomal fraction of the whole brain from morphine-dependent rats exhibited an increase in cyclic AMP which was accompanied by elevated adenylate cyclase and protein kinase activity. Naloxone administration suppressed this rise in cyclic AMP and reversed the morphine-stimulated increases in the activities of adenylate cyclase and protein kinase. Following the withdrawal of morphine treatment, alterations in cyclic AMP metabolism were similar to those noted in morphine-naloxone group. Furthermore, substitution of morphine with methadone antagonized the observed alterations in cyclic nucleotide metabolism during withdrawal.
AB - Effects of morphine administration were studied on cyclic AMP metabolism in several regions of rat brain. In the cortex, cerebellum and thalamus-hypothalamus, morphine dependence did not alter the activity of either adenylate cyclase or phosphodiesterase. However, during withdrawal from the opiate treatment, adenylate cyclase activity declined in all three regions studied. In contrast, the striatal cyclic AMP metabolism was enhanced during morphine treatment as reflected by elevated endogenous cyclic AMP and increased adenylate cyclase. Furthermore, narcotic dependence produced significant increases in acetylcholinesterase activity of rat striatum. Whereas morphine withdrawal reversed the changes in striatal acetylcholine levels and acetylcholinesterase activity, the enhanced striatal dopamine remained unaltered. Although the activity of striatal adenylate cyclase was significantly reduced when compared to the morphine-dependent rats, the drop in cyclic AMP levels was not significant. Methadone replacement did not affect the changes in striatal dopamine seen in morphine-withdrawn rats. Whereas dopamine stimulated equally well the striatal adenylate cyclase from control or morphine-dependent animals, it failed to stimulate the striatal enzyme from rats undergoing withdrawal. The crude synaptosomal fraction of the whole brain from morphine-dependent rats exhibited an increase in cyclic AMP which was accompanied by elevated adenylate cyclase and protein kinase activity. Naloxone administration suppressed this rise in cyclic AMP and reversed the morphine-stimulated increases in the activities of adenylate cyclase and protein kinase. Following the withdrawal of morphine treatment, alterations in cyclic AMP metabolism were similar to those noted in morphine-naloxone group. Furthermore, substitution of morphine with methadone antagonized the observed alterations in cyclic nucleotide metabolism during withdrawal.
UR - http://www.scopus.com/inward/record.url?scp=0016803313&partnerID=8YFLogxK
U2 - 10.1016/0024-3205(75)90297-0
DO - 10.1016/0024-3205(75)90297-0
M3 - Article
C2 - 168451
AN - SCOPUS:0016803313
SN - 0024-3205
VL - 16
SP - 1889
EP - 1894
JO - Life Sciences
JF - Life Sciences
IS - 12
ER -