Galanthamine does not attenuate attentional or temporal impairments subsequent to cholinergic deaffe

1
Galanthamine does not attenuate attentional or
temporal impairments subsequent to cholinergic
deafferentation of the cortex or hippocampus
M.M. Martin S.L. Weathered S.J. Wagner D.G.
WallaceDept Psychology, Northern Illinois Univ,
DeKalb IL, USA
742.6
Abstract
Results
Results
DODGE BRACE
The role of the basal forebrain cholinergic
system in early symptomology of dementia of the
Alzheimers type (DAT) remains an area of intense
debate. Although involvement of the
basalocortical cholinergic system in attentional
processing has been established, function of the
septohippocampal cholinergic system remains to be
determined. A recent study demonstrated a double
dissociation between these systems in the
organization of rat food protection behavior that
may parallel the attentional impairments and
temporal disorientation observed during the early
stages of DAT. The current study sought to
examine whether an acetylcholinesterase inhibitor
currently used for the treatment of DAT (i.e.,
galanthamine) could attenuate these deficits.
Figure 2 Example topographies of dodging (left
panels) and bracing (right panels) food
protection behaviors are plotted with a dodger
(blue) and robber (red). Initial body positions
are indicated by black lines. The
moment-to-moment speeds are plotted for each
rats head during a dodge and brace (bottom
panels). Dodging behavior results in a dramatic
increase in speed and distance between heads. In
contrast, bracing behavior is slower and results
in a smaller terminal distance between heads.
Figure 5 Mean times spent engaged in food
protection behaviors are shown for MS (left
panel) and NB (right panel) groups. Times spent
dodging (circles) and bracing (triangles) are
plotted for SAL (open symbols) and GAL (closed
symbols) treated rats. Drug condition had no
effect on either group. Note that there is a lack
of transition between time spent dodging and
bracing for the MS groups (left panel), whereas
the NB groups (right panel) exhibited a
transition between primarily dodging in early
samples to both dodging and bracing in late
samples.
Method
Figure 3 Total number of food protection
behaviors (left panel) and percentage of
successful behaviors (right panel) are shown for
each drug condition and lesion type. Number of
food protection behaviors did not differ by drug
condition or lesion type. Drug condition also had
no influence on percent of successful food
protection however, the NB groups were less
successful in protecting food relative to the MS
groups.
Long Evans female rats received injections of 192
IgG-Saporin (SAP) into the nucleus basalis (NB)
or medial septum (MS). Rats in each lesion group
were assigned to receive saline (SAL) or 3.0
mg/kg galanthamine (GAL) s.c. twice daily.
Subsequent to recovery, rats (dodgers) were
placed into an enclosure and provided a hazelnut
in the presence of an unoperated conspecific
(robber). All dodger rats engaged in food
protection behaviors, such as dodging or bracing,
to prevent the theft of the hazelnut. Several
measures were analyzed to reflect attentional,
motivational, and temporal influences on behavior.
Conclusions

• Results of this study are consistent with
  previous research, with a double dissociation in
  roles of the basalocortical and septohippocampal
  cholinergic systems in organization of food
  protection behaviors.
• NB groups were significantly worse at protecting
  their food, although their behaviors remained
  temporally organized.
• MS groups displayed temporal disorganization of
  food protection behaviors, as evidenced in the
  lack of transition observed between time spent
  dodging and bracing for MS groups.
• Impairments in both groups persisted after
  administration of GAL.
• Results of this study suggest that the modest
  benefits afforded by galanthamine administration
  in DAT patients may not reflect improved
  attention or temporal orientation.

Figure 1 Photographs of coronal sections
stained for AChE are presented from
representative MS SAL, MS GAL, NB SAL, and NB GAL
rats (left panel). GAL resulted in an increased
cortical staining in the MS GAL rats relative to
MS SAL rats (middle panel) but had no effect in
the NB groups (right panel).
Figure 4 Average dodger speeds are shown for MS
(left panel) and NB (right panel) groups. Dodging
(circles) and bracing (triangles) speeds are
plotted for SAL (open symbols) and GAL (closed
symbols) treated rats. Drug condition and lesion
type had no effect on speed, and overall, rats
reached higher speeds when engaging in dodging
relative to bracing behaviors.
MS SAL MS GAL NB
SAL NB GAL
Correspondence M. Martin
meganstp_at_umich.edu D. Wallace dwallace_at_niu.edu
Web www.niu.edu/user/tj0dgw1 Support
Contributed By NINDS grant NS051218 (D
Wallace) 2007 APA Dissertation Research Award (M
Martin)