Involvement of cyclic AMP at the level of the nucleus reticularis pontis caudalis in the acoustic startle response.
Rats were implanted with cannulas in the nucleus reticularis pontis caudalis (PnC), an obligatory part of the neural pathway that mediates the acoustic startle reflex. Following at least 1 week of recovery, rats were tested for acoustic startle amplitude before or after infusion of compounds known to alter the second messenger, adenosine cyclic 3', 5'-monophosphate (cAMP). Local infusion into the PnC of the cAMP analog, 8-bromo cAMP (0.125-1.0 micrograms), increased the amplitude of the acoustic startle response in a dose-dependent manner. In addition, local infusion of a phosphodiesterase inhibitor, rolipram (10 micrograms) or the water soluble adenylate cyclase activator, forskolin-DHA (2.5 micrograms), produced a significant enhancement of startle amplitude. These effects probably resulted from intracellular actions because cAMP itself, which does not readily penetrate lipid membranes, had no effect. Moreover, the effects seemed somewhat specific because the precursor of cAMP, ATP or 8-bromo cGMP, also failed to alter startle at doses where 8 bromo-cAMP did. The fact that a phosphodiesterase inhibitor elevated startle suggests that cAMP serves to tonically elevate startle at this level of the pathway. Hence, treatments that either increase (fear, sensitization) or decrease (habituation, pre-pulse inhibition) startle at the level of the PnC may do so via release of neurotransmitters either positively or negatively coupled to cAMP, which in turn may alter either sound evoked transmitter release, excitability of PnC neurons or both.
de Lima
T C
TC
Yale University School of Medicine, Department of Psychiatry, New Haven, CT 06508, USA.
Davis
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M
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000161:Acoustic Stimulation; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004224:Diterpenes; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D012154:Reticular Formation / Q000187:drug effects*
C099386:7b-deacetyl-7b-(gamma-(morpholino)butyryl)forskolin; D004224:Diterpenes; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D006152:Cyclic GMP