Extinction Learning Deficit in a Rodent Model of Attention-Deficit Hyperactivity Disorder

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Description

Background: Deficient operant extinction has been hypothesized to be constitutive of ADHD dysfunction. In order to elucidate the behavioral mechanisms underlying this deficit, the performance of an animal model of ADHD, the spontaneously hypertensive rat (SHR), was compared against the performance

Background: Deficient operant extinction has been hypothesized to be constitutive of ADHD dysfunction. In order to elucidate the behavioral mechanisms underlying this deficit, the performance of an animal model of ADHD, the spontaneously hypertensive rat (SHR), was compared against the performance of a control strain, the Wistar-Kyoto rat (WKY) during extinction.

Method: Following extensive training of lever pressing under variable interval schedules of food reinforcement (reported previously), SHR and WKY rats were exposed to two sessions of extinction training. Extinction data was analyzed using the Dynamic Bi-Exponential Refractory Model (DBERM) of operant performance. DBERM assumes that operant responses are organized in bouts separated by pauses; during extinction, bouts may decline across multiple dimensions, including frequency and length. DBERM parameters were estimated using hierarchical Bayesian modeling.

Results: SHR responded more than WKY during the first extinction session. DBERM parameter estimates revealed that, at the onset of extinction, SHR produced more response bouts than WKY. Over the course of extinction, response bouts progressively shortened for WKY but not for SHR.

Conclusions: Based on prior findings on the sensitivity of DBERM parameters to motivational and schedule manipulations, present data suggests that (1) more frequent response bouts in SHR are likely related to greater incentive motivation, and (2) the persistent length of bouts in SHR are likely related to a slower updating of the response-outcome association. Overall, these findings suggest specific motivational and learning deficits that may explain ADHD-related impairments in operant performance.

Date Created
2012-12-13
Agent

Characterizing Operant Hyperactivity in the Spontaneously Hypertensive Rat

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Description

Background: Operant hyperactivity, the emission of reinforced responses at an inordinately high rate, has been reported in children with ADHD and in the Spontaneously Hypertensive Rat (SHR), the most widely studied animal model of ADHD. The SHR emits behavior at hyperactive

Background: Operant hyperactivity, the emission of reinforced responses at an inordinately high rate, has been reported in children with ADHD and in the Spontaneously Hypertensive Rat (SHR), the most widely studied animal model of ADHD. The SHR emits behavior at hyperactive levels, relative to a normoactive strain, only when such behavior is seldom reinforced. Because of its dependence on rate of reinforcement, operant hyperactivity appears to be driven primarily by incentive motivation, not motoric capacity. This claim was evaluated in the present study using a novel strategy, based on the organization of behavior in bouts of reinforced responses separated by pauses.

Method: Male SHR, Wistar-Kyoto (WKY) and Wistar rats (WIS) were exposed each to a multiple variable-interval schedule of sucrose reinforcement (12, 24, 48, 96, and 192 s) between post-natal days (PND) 48 and 93. Responding in each schedule was examined in two epochs, PND 58-62 and 89-93. Parameters of response-reinforcement functions (Herrnstein's hyperbola) and bout-organized behavior were estimated in each epoch.

Results: SHR emitted higher response rates than WKY and WIS, but only when rate of reinforcement was low (fewer than 2 reinforcers per minute), and particularly in the second epoch. Estimates of Herrnstein's hyperbola parameters suggested the primacy of motivational over motoric factors driving the response-rate differential. Across epochs and schedules, a more detailed analysis of response bouts by SHR revealed that these were shorter than those by WKY, but more frequent than those by WKY and WIS. Differences in bout length subsided between epochs, but differences in bout-initiation rate were exacerbated. These results were interpreted in light of robust evidence linking changes in bout-organization parameters and experimental manipulations of motivation and response-reinforcement contingency.

Conclusions: Operant hyperactivity in SHR was confirmed. Although incentive motivation appears to play an important role in operant hyperactivity and motoric capacity cannot be ruled out as a factor, response-bout patterns suggest that operant hyperactivity is primarily driven by steeper delay-of-reinforcement gradients. Convergence of this conclusion with theoretical accounts of ADHD and with free-operant performance in children with ADHD supports the use of SHR as an animal model of ADHD.

Date Created
2012-01-26
Agent