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Format:
Print
Author:
Thanellou, Alexandra
Dept./Program:
Psychology
Year:
2010
Degree:
PhD
Abstract:
Subjects with ADHD and male spontaneously hypertensive rats (SHR, an animal model of ADHD) exhibit timing deficits in eyeblink conditioning. However, SHRs are not only hyperactive but are also hypertensive. We used Wistar-Kyoto Hyperactive (WKHA) and Wistar-Kyoto Hypertensive (WKHT) rats (males/females) to evaluate whether behavioral deficits in eyeblink conditioning seen in SHRs are specific to hyperactivity. In Experiment 1, we used a long-delay (750-ms) eyeblink conditioning task in which a tone CS was paired with a periorbital stimulation US. WKHAs and WKHTs acquired and extinguished CRs similarly. However, only WKHA males displayed an inability to develop inhibition of delay (laD; defined as a concentration of conditioned responding in the later part of the CS and an increase in CR latency as learning progresses) compared to WKHTs. Experiment 2 consisted of explicitly unpaired presentations of the CS and the US to rule out the possibility that nonassociative responding to the stimuli was different between the two strains.
These results further validate the hypothesis of cerebellar abnormalities in an animal model of ADHD-like symptoms that does not also exhibit hypertension, and suggest the possibility that behavioral impairments in WKHAs and SHRs may be due to a deficit in IOD. In Experiments 3-5, we examined whether IOD can be explained by the development of conditioned inhibition in the early part of the CS. In Experiments 3 and 4 we trained animals with a 750-ms delay task (15 sessions). Subsequently, animals were tested using a retardation test (5 sessions; trials consisted of a 765-ms tone CS with the US delivered 250 ms after CS onset). In both Experiments 3 and 4, experimental animals trained with the 750-ms delay task (Delay Tone groups) exhibited IOD during acquisition. Subsequent acquisition of the shortened CS-US interval was faster in the Delay Tone groups compared to the Sit and Latent Inhibition control groups (Experiment 3), or compared to the Light Delay and Sit control groups (Experiment 4). In Experiment 5, two groups were trained for 15 sessions with two. trial types. Subsequently, both groups underwent a summation test (1 session).
The Experimental group showed more (not fewer) CRs when an excitor occurred early in the CS compared to when the excitor was presented alone. Results in Experiments 3-5 suggest that 100 does not involve conditioned inhibition and that CRs present early in conditioning during the early part of a long CS may be subject to rapid reacquisition later, making 100 more like an extinction phenomenon. In Experiment 6, we directly investigated whether an inability to develop IOD underlies the behavioral deficits seen in WKHAs using a retardation test (as in Experiments 3 and 4). Animals from all strains trained during acquisition with a tone CS exhibited faster acquisition to the shortened CSUS interval during retardation (testing). In Experiment 7 we estimated numbers of Purkinje and granule cells to examine whether differences in the numbers of these cerebellar neuronal populations are responsible for the deficits in the development of 10D seen WKHAs. Our results indicated that WKHAs have more granule cells than Wistars and WKHTs and more Purkinje cells than Wistars. We propose that greater numbers of granule cells interfere with the inherent propensity of the circuit to subserve a timevarying CS representation.