Prenatal exposure to cocaine decreases adenylyl cyclase activity in embryonic mouse striatum.
Adenylyl cyclase activity was measured in the striatum of naive mice as a function of age and in mice exposed in utero to cocaine. In naive Swiss-Webster mice, basal and forskolin-stimulated adenylyl cyclase activity increased gradually from embryonic day 13 (E13) until 2-3 weeks of age when activity peaked before decreasing slightly to adult levels. The ability of the dopamine D1 receptor agonist, SKF 82958, to stimulate adenylyl cyclase activity also increased in magnitude until P15. In a separate study, pregnant Swiss-Webster mice were injected twice daily with cocaine (15 mg/kg, s.c.) or an equal volume of saline from E10 to E17. Adenylyl cyclase activity was measured in the striatum of E18 embryos. Basal adenylyl cyclase activity was significantly reduced following prenatal exposure to cocaine. Likewise, the ability of forskolin or SKF 82958 to stimulate adenylyl cyclase was attenuated following cocaine exposure. DeltaFosB was not induced, contrary to what is seen in adult mice. These results demonstrate a functional change in a critical signal transduction pathway following chronic in utero exposure to cocaine that might have profound effects of the development of the brain. Alterations in the cAMP system may underlie some of the deficits seen in humans exposed in utero to cocaine.
Unterwald
Ellen M
EM
Department of Pharmacology, Temple University School of Medicine, 3420 N. Broad St., Philadelphia, PA 19140, USA. ellen.unterwald@temple.edu
Ivkovic
Sanja
S
Cuntapay
Marie
M
Stroppolo
Antonella
A
Guinea
Barbara
B
Ehrlich
Michelle E
ME
D000199:Actins / Q000096:biosynthesis; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D003042:Cocaine / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D005260:Female; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D017072:Neostriatum / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology*; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins / Q000096:biosynthesis; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis
D000199:Actins; D050483:Dopamine Plasma Membrane Transport Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D016760:Proto-Oncogene Proteins c-fos; D020928:Mitogen-Activated Protein Kinases; D000262:Adenylyl Cyclases; D003042:Cocaine; D004298:Dopamine