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, 164, 107041

Age-related Differences in Appetitive Trace Conditioning and Novel Object Recognition Procedures

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Age-related Differences in Appetitive Trace Conditioning and Novel Object Recognition Procedures

Hayley J Marshall et al. Neurobiol Learn Mem.

Abstract

Appetitive trace conditioning (TC) was examined over 6 months in younger-adult (2-8 months) and middle-aged (12-18 months) male Wistar RccHan rats, to test for early age-related impairment in working memory. Novel object recognition (NOR) was included as a comparison task, to provide a positive control in the event that the expected impairment in TC was not demonstrated. The results showed that TC improved at both ages at the 2 s but not at the 10 s trace interval. There was, however, evidence for reduced improvement from one day to the next in the middle-aged cohort tested with the 2 s trace conditioned stimulus. Moreover, within the 10 s trace, responding progressively distributed later in the trace interval, in the younger-adult but not the middle-aged cohort. Middle-aged rats showed NOR discriminative impairment at a 24 h but not at a 10 min retention interval. Object exploration was overall reduced in middle-aged rats and further reduced longitudinally. At the end of the study, assessing neurochemistry by HPLC-ED showed reduced 5-HIAA/5-HT in the dorsal striatum of the middle-aged rats and some correlations between striatal 5-HIAA/5-HT and activity parameters. Overall the results suggest that, taken in isolation, age-related impairments may be overcome by experience. This recovery in performance was seen despite the drop in activity levels in older animals, which might be expected to contribute to cognitive decline.

Keywords: Dorsal striatum; HPLC-ED; Medial prefrontal cortex; Nucleus accumbens; Rat; Trace conditioning.

Figures

Fig. 1
Fig. 1
Mean nose-poke responding (±sem) during (A) the inter-trial-interval (ITI), (B) the 5 s after food unconditioned stimulus (US) delivery, or (C) the 5 s presentations of the conditioned stimulus (CS) in middle-aged and younger-adult cohorts of Wistar RccHan rats N = 9–12/cell. Asterisks indicate the significant difference between the age groups at timepoint 1 in the 2 s trace group, averaged across days, **p < 0.01). Hashtags indicate the significant difference between the age groups at timepoint 1, averaged across days and trace intervals, ##p < 0.01).
Fig. 2
Fig. 2
Mean nose-pokes during CS presentations are shown as a function of the 6 blocks of trials conducted on each of two days at timepoint 1 for (A) the middle-aged cohort and (B) the younger-adult cohort. Solid black lines denote rats conditioned at the 2 s trace interval and broken grey lines denote rats conditioned at the 10 s trace interval. Triangles denote day 1 conditioning and X symbols denote day 2 conditioning. Error bars represent the standard error of the mean. Asterisks indicate a significant difference between day 1 and day 2 responding for the 2 s trace conditioned groups, *p < 0.05, **p < 0.01, ***p < 0.001.
Fig. 3
Fig. 3
Mean nose-pokes during the five 2 s bins of the 10 s trace interval for the middle-aged cohort (darker greys) and the younger-adult cohort (lighter greys) and timepoint 1 (in each case a relatively darker shade) versus timepoint 5 (in each case a relatively lighter shade). Error bars represent the standard error of the mean. Asterisk indicates a significant difference between the timepoints (the younger-adult cohort bin 1), *p < 0.05.
Fig. 4
Fig. 4
Total sample stage object exploration (s) at each of the two NOR test timepoints. Tests at timepoint 1 (dark grey bars) were conducted at 56 (the middle-aged cohort) and 12 weeks (the younger-adult cohort). Tests at timepoint 5 (light grey bars) were conducted at 79 (the middle aged cohort) and 35 weeks (the younger-adult cohort). Error bars represent the standard error of the mean. Asterisks show significant differences between timepoints, ***p < 0.001. Hashtags show significant differences between age groups at the corresponding timepoints, #p < 0.05, ###p < 0.001.
Fig. 5
Fig. 5
Discrimination ratio scores at each of the two NOR test timepoints. A ratio of 0.5 indicates no discrimination; scores above 0.5 indicate a preference for the novel object. Tests at timepoint 1 (dark grey bars) were conducted at 56 (the middle-aged cohort) and 12 weeks (the younger-adult cohort). Tests at timepoint 5 (light grey bars) were conducted at 79 (the middle-aged cohort) and 35 weeks (the younger-adult cohort). Error bars represent the standard error of the mean. Asterisks show performance significantly above the ratio 0.5, *p < 0.05, **p < 0.01, ***p < 0.001.
Fig. 6
Fig. 6
The 5-HT/5-HIAA ratio showing (A) the relative reduction in the dorsal striatum of rats aged 18.5 (as compared with 8.5) months at the end of the experiment, (B) the correlation between the 5-HT/5-HIAA ratio in dorsal striatum and novel object exploration at timepoint 5, and (C) the correlation between the 5-HT/5-HIAA ratio in the NAc and responding in the ITI at the final timepoint. Asterisk shows the significant reduction in the dorsal striatum of the middle-aged cohort (now aged 18.5 months) as compared to the relatively younger group (now aged 8.5 months), *p < 0.05.

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