Selective D1 agonism but not D2 antagonism is reflected in cAMP and cGMP levels in rat CSF.
Cyclic adenosine 3'5'-monophosphate (cAMP) and cyclic guanosine 3'5'-monophosphate (cGMP) serve as second messengers in several cellular pathways within the central nervous system. In various neurological and psychiatric disorders with known deficits in neurotransmission function, CSF levels of cAMP and/or cGMP in patients were studied. Very little information is currently available on cAMP and cGMP levels in CSF of animals. Moreover, this is the first study on the effects of pharmacological treatment on cAMP and cGMP levels in rat CSF. Effect of systemic treatment with a D1 receptor agonist SKF82958 and a D2 receptor antagonist haloperidol on cAMP and cGMP levels, as well as baseline cAMP and cGMP levels in CSF of rats was determined. A significantly increased cAMP and cGMP level in cisternal CSF of rats systemically treated with the D1 receptor agonist SKF82958 was observed, while when treated with the D2 antagonist haloperidol, no effect on cAMP and only a slight decrease of cGMP was observed after treatment with the highest dose. Determining cAMP and/or cGMP in CSF of experimental animals can serve as a useful tool to study neural processes affected by disease and treatment.
Torremans
An
A
Johnson & Johnson Pharmaceutical Research and Development, A Division of Janssen Pharmaceutica NV, 2340 Beerse, Antwerp, Belgium. antorremans@hotmail.com
Van Hemelrijck
An
A
Straetemans
Roel
R
Vanhoof
Greet
G
Van Den Kieboom
Gerd
G
Drinkenburg
Wilhelmus H
WH
D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D002555:Cerebrospinal Fluid / Q000187:drug effects*; D000242:Cyclic AMP / Q000134:cerebrospinal fluid*; D006152:Cyclic GMP / Q000134:cerebrospinal fluid*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; C071262:SK&F 82958; D000242:Cyclic AMP; D006152:Cyclic GMP; D006220:Haloperidol