Transcript Style E 36 by 54 - Northern Illinois University

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. Wallace
Dept Psychology, Northern Illinois Univ, DeKalb IL, USA
Results
50
40
30
20
10
120
100
100
MS GAL
NB SAL
80
*
80
60
60
40
40
20
0
NBSAL
NBGAL
MSSAL
MSGAL
Cortex
Hipp
Brain region
NB GAL
Cortex
20
0
Hipp
Brain region
Optical density
120
Optical density
MS SAL
NB
SAL
GAL
SAL
MS
0.6
0.4
0.4
0.2
0.2
0.0
0.0
0.1
0.3
0.5
0.0
0.1
0.3
Time (s)
4
3
5
4
3
2
*
*
2
1
1
0
0
Early
Late
Sample
Early
Late
Sample
90
• 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.
80
70
60
50
GAL
SAL
MS
MS
GAL
NB
NB
0.5
Dodge (SAL)
Brace (SAL)
Dodge (GAL)
Brace (GAL)
0.4
0.3
0.5
0.4
0.3
*
*
0.1
0.2
0.1
0.0
0.0
Sample
Dodge (SAL)
Brace (SAL)
Dodge (GAL)
Brace (GAL)
Conclusions
100
SAL
Late
5
0.5
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.
Early
NB
0.0
Time (s)
GAL
0.2
MS
Time (s)
0.6
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.
Time (s)
Speed (m/s)
0.8
NB
Speed (m/s)
MS
0.8
*
0
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).
0.5m
Early
Late
Sample
Speed (m/s)
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.
BRACE
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.
% Successful Behaviors
Method
DODGE
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 rat’s 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.
# Behaviors
The role of the basal forebrain cholinergic system in early symptomology of
dementia of the Alzheimer’s 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.
Results
Speed (m/s)
Abstract
742.6
• 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.
Correspondence:
M. Martin
[email protected]
D. Wallace
[email protected]
Web:
www.niu.edu/user/tj0dgw1
Support Contributed By:
NINDS grant NS051218 (D Wallace)
2007 APA Dissertation Research Award (M Martin)