Effects of the phosphodiesterase inhibitor rolipram on the acoustic startle response in rats.
Systemic administration of the phosphodiesterase inhibitor rolipram (0.05-10.0 mg/kg, IP) produced a rapid and dose-related increase in the amplitude of the acoustic startle response in rats. The (-) isomer was more potent than the (+) isomer in enhancing startle amplitude. Rolipram increased startle responses that were elicited by brief electrical stimulation of the ventral cochlear nucleus or nucleus reticularis pontis caudalis, two brainstem relay nuclei of the startle neural circuit. A low (5 micrograms) dose of rolipram produced an excitatory effect on startle following spinal (lumbar intrathecal) infusion but not following supraspinal (lateral ventricle) infusion. Rolipram (0.5 mg/kg, IP) excitation of startle was not blocked by drugs which differentially disrupt the release of monoamines (DSP4, reserpine + alpha-methyl-para-tyrosine, reserpine + para-chloro-phenylalanine) or by drugs which differentially block monoamine receptors (haloperidol, prazosin, idazoxan, cinanserin, or cyproheptadine). The marked increase in startle seen following systemic rolipram injection is attributable, at least in part, to an action in the lumbar spinal cord that directly or indirectly facilitates neural transmission along the reticulospinal component of the startle reflex neural pathway. The startle reflex should be a useful behavioral test system for studying the mechanism of action of rolipram and related compounds purported to selectively inhibit calmodulin-independent forms of phosphodiesterase.
Kehne
J H
JH
Yale University School of Medicine, Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven.
Boulis
N M
NM
Davis
M
M
D000161:Acoustic Stimulation; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013216:Reflex, Startle / Q000187:drug effects*; D020889:Rolipram; D013237:Stereoisomerism; D013566:Sympathomimetics / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D013566:Sympathomimetics; D000242:Cyclic AMP; D020889:Rolipram