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Alcohol Withdrawal Increases Protein Kinase A Activity in the Rat Inferior Colliculus
Author(s) -
Akinfiresoye Luli R.,
Miranda Clive,
Lovinger David M.,
N'Gouemo Prosper
Publication year - 2016
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13223
Subject(s) - alcohol , protein kinase a , ethanol , inferior colliculus , stimulation , chemistry , medicine , pharmacology , endocrinology , kinase , anesthesia , biochemistry , nucleus , psychiatry
Background Cyclic AMP ‐dependent protein kinase A ( PKA ) signaling is a key target for the action of alcohol and may therefore play a role in the pathophysiology of alcohol withdrawal seizures ( AWS s). Here, we investigated the role of PKA activity with respect to increased seizure susceptibility in rats that were subjected to alcohol withdrawal. Methods Adult male Sprague Dawley rats received 3 daily doses of ethanol (EtOH) (or vehicle) for 4 consecutive days. Rats were then tested for susceptibility to acoustically evoked AWS s 3, 24, and 48 hours after the last alcohol dose. In separate experiments, the inferior colliculus ( IC ) was collected at these same time points from rats subjected to alcohol withdrawal and control rats following alcohol withdrawal. PKA activity, catalytic C α ( PKA C α ) protein, regulatory RII α ( PKA RII α ) protein, and RII β ( PKA RII β ) protein were measured in the IC . Lastly, in situ pharmacological studies were performed to evaluate whether inhibiting PKA activity in the IC suppressed AWS s. Results In the EtOH‐treated group, AWS s were observed at the 24‐hour time point, but not at the 3‐hour or 48‐hour time points. In the IC , PKA activity was significantly higher both 3 hours (i.e., before AWS susceptibility) and 24 hours after the last alcohol dose (when AWS susceptibility peaked) than in control rats. Consistent with these findings, protein levels of the PKA C α subunit were significantly increased in the IC both 3 and 24 hours after the last alcohol dose. Lastly, in situ inhibition of PKA activity within the IC suppressed AWS s. Conclusions The increase in PKA activity and PKA C α protein expression in the IC preceded the occurrence of AWS s, and inhibiting PKA activity within the IC suppressed acoustically evoked AWS s. Together, these findings suggest that altered PKA activity plays a key role in the pathogenesis of AWS s.