Paige Beck
PBBeck@uams.edu
We recorded the effects of administration of the stimulant modafinil on
the amplitude of the sleep state-dependent auditory P13 evoked potential
in freely moving rats, a measure of arousal that is thought to be
generated by the cholinergic arm of the reticular activating system,
specifically the pedunculopontine nucleus (PPN). Groups of rats
were implanted for recording auditory evoked responses and the effects
on P13 potential amplitude of intracranial injections into the PPN of
neuroactive agents determined. The effects of intracranial injections
into the PPN of modafinil showed that P13 potential amplitude increased
in a dose-dependent manner at doses of 100, 200 and 300 microM. The
effect was blocked by pretreatment with either of the gap junction
antagonists carbenoxolone (300 microM) or mefloquine (25 microM), which
by themselves slightly decreased P13 potential amplitude. These
results suggest that modafinil increases arousal levels as determined by
the amplitude of the P13 potential, an effect blocked by gap junction
antagonists, suggesting that one mechanism by which modafinil increases
arousal may be by increasing electrical coupling.
A B
Effects of the
gap junction antagonists on MOD-induced changes on P13 potential
amplitude. A.
Percent change in
average P13 potential amplitude after saline (X), and after MOD at 300
microM, as well as after CBX alone at 300 microM (filled triangles) and
CBX at 300 microM followed 20 min later by MOD at 300 microM (open
triangles) compared to pre-injection control for each agent. CBX alone
(filled triangles) induced transient decreases compared to saline alone
at 10, 25 and 55 min (p<0.01, asterisks not shown for clarity), while
pretreatment with CBX blocked the effects of MOD at all time points
(open triangles) and was not different from saline (X). When a three
factor, two way analysis between MOD at 300 microM (filled circles), CBX
at 300 microM (filled triangles) and CBX+MOD (open triangles) was done
(pre- and post injection values at all time points after MOD vs CBX vs
CBX+MOD), significant increases were present for MOD vs CBX+MOD at 25,
35 and 55 min (** p<0.01), as well as 45 min (*p<0.05) (upper asterisks
in figure 2A), suggesting the presence of CBX suppressed the increases
seen with MOD alone. Comparison between CBX and CBX+MOD showed only
significance at 10 min (*p<0.05, asterisk at bottom of figure 2A).
Significant differences between MOD alone and CBX alone were present at
10-55 min (p<0.01, asterisks not shown for clarity). B. Percent
change in average P13 potential amplitude after saline (X), and after
MOD at 300 microM (filled circles), as well as after MEF alone at 25
microM (filled squares) and MEF at 25 microM followed 20 min later by
MOD at 300 microM (open squares) compared to pre-injection control for
each agent. One-way ANOVA comparison between MEF alone and saline
induced significant decreases at 5, 10, 15, 25, 35 ( p<0.01), and 45 min
(p<0.05) (asterisks not shown for clarity), but pretreatment with MEF
blocked the effects of MOD at all time points (open squares) and was not
different from saline (X). When a three factor, Two way analysis (pre-
and post injection values at all time points after MOD vs MEF vs MEF+MOD
between MOD at 300 microM (filled circles) and MEF+MOD (open squares)
was done, significant increases were present comparing MOD vs MEF+MOD at
10 and 15 min (*p<0.05) and 25-55 min (** p<0.01) (upper asterisks in
figure 2B), suggesting the presence of MEF suppressed the increases seen
with MOD alone. When MEF vs MEF+MOD were compared, significant
decreases were present only at 10 and 35 min (**p<0.01) (lower asterisks
in figure 2B). Significant differences between MOD alone and MEF alone
were present at 10-55 min (p<0.01, asterisks not shown for clarity). |
