Extinction learning deficit in a rodent model of attention-deficit hyperactivity disorder

Behavioral and Brain Functions

Ryan J Brackney¹  Timothy HC Cheung¹  Katrina Herbst¹  Jade C Hill¹  Federico Sanabria¹ 

[1] Arizona State University, P.O. Box 871104, Tempe, AZ, 85287-1104, USA

关键词: Dynamic Bi-Exponential Refractory Model (DBERM);    Response-outcome association;    Motivation;    Learning;    Hierarchical model;    ADHD;    SHR;    Extinction;    Bout;    Variable interval;   

Others  :  793796
DOI  :  10.1186/1744-9081-8-59

 received in 2012-03-05, accepted in 2012-11-25,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Brackney et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Hill JC, Herbst K, Sanabria F: Characterizing Operant Hyperactivity in the Spontaneously Hypertensive Rat. Behav Brain Funct 2012, 8:5. BioMed Central Full Text
• [2]Luman M, Tripp G, Scheres A: Identifying the neurobiology of altered reinforcement sensitivity in ADHD: a review and research agenda. Neurosci Biobehav R 2010, 34:744-754.
• [3]Johansen EB, Aase H, Meyer A, Sagvolden T: Attention-deficit/hyperactivity disorder (ADHD) behaviour explained by dysfunctioning reinforcement and extinction processes. Behav Brain Res 2002, 130:37-45.
• [4]Tripp G, Wickens JR: Research review: dopamine transfer deficit: a neurobiological theory of altered reinforcement mechanisms in ADHD. J Child Psychol Psyc 2008, 49:691-704.
• [5]Sagvolden T, Johansen EB, Aase H, Russell VA: A dynamic developmental theory of attention-deficit/hyperactivity disorder (ADHD) predominantly hyperactive/impulsive and combined subtypes. Behav Brain Sc 2005, 28:397-419. discussion 419–68
• [6]Douglas VI, Parry PA: Effects of reward and nonreward on frustration and attention in attention deficit disorder. J Abnorm Child Psych 1994, 22:281-302.
• [7]Iaboni F, Douglas VI, Ditto B: Psychophysiological response of ADHD children to reward and extinction. Psychophysiology 1997, 34:116-123.
• [8]Wigal T, Swanson JM, Douglas VI, Wigal SB, Wippler CM, Cavoto KF: Effect of reinforcement on facial responsivity and persistence in children with attention-deficit hyperactivity disorder. Behav Modif 1998, 22:143.
• [9]Itami S, Uno H: Orbitofrontal cortex dysfunction in attention-deficit hyperactivity disorder revealed by reversal and extinction tasks. Neuroreport 2002, 13:2453.
• [10]Frings M, Gaertner K, Buderath P, Gerwig M, Christiansen H, Schoch B, Gizewski ER, Hebebrand J, Timmann D: Timing of conditioned eyeblink responses is impaired in children with attention-deficit/hyperactivity disorder. Exp Brain Res 2010, 201:167-176.
• [11]Sagvolden T, Johansen EB, Wøien G, Walaas SI, Storm-Mathisen J, Bergersen LH, Hvalby O, Jensen V, Aase H, Russell VA, Killeen PR, Dasbanerjee T, Middleton FA, Faraone SV: The spontaneously hypertensive rat model of ADHD--the importance of selecting the appropriate reference strain. Neuropharmacology 2009, 57:619-626.
• [12]Sagvolden T, Hendley ED, Knardahl S: Behavior of hypertensive and hyperactive rat strains: Hyperactivity is not unitarily determined. Physiol Behav 1992, 52:49-57.
• [13]Johansen EB, Sagvolden T: Behavioral effects of intra-cranial self-stimulation in an animal model of attention-deficit/hyperactivity disorder (ADHD). Behav Brain Res 2005, 162:32-46.
• [14]Guttman N: Operant conditioning, extinction, and periodic reinforcement in relation to concentration of sucrose used as reinforcing agent. J Exp Psychol 1953, 46:213.
• [15]Alsop B: Problems with spontaneously hypertensive rats (SHR) as a model of attention-deficit/hyperactivity disorder (AD/HD). J Neurosci Meth 2007, 162:42-48.
• [16]Podlesnik CA, Jimenez-Gomez C, Ward RD, Shahan TA: Resistance to change of responding maintained by unsignaled delays to reinforcement: A response-bout analysis. J Exp Anal Behav 2006, 85:329.
• [17]Shull RL, Gaynor ST, Grimes JA: Response rate viewed as engagement bouts: resistance to extinction. J Exp Anal Behav 2002, 77:211.
• [18]Brackney RJ, Cheung THC, Neisewander JL, Sanabria F: The isolation of motivational, motoric, and schedule effects on operant performance: A modeling approach. J Exp Anal Behav 2011, 96:17-38.
• [19]Cheung THC, Neisewander JL, Sanabria F: Extinction under a behavioral microscope: isolating the sources of decline in operant response rate. Behav Process 2012, 90:111-123.
• [20]Shull RL, Gaynor ST, Grimes JA: Response rate viewed as engagement bouts: effects of relative reinforcement and schedule type. J Exp Anal Behav 2001, 75:247.
• [21]Catania AC: The operant reserve: a computer simulation in (accelerated) real time. Behav Process 2005, 69:257-278.
• [22]Gelman A: Bayesian data analysis. London: CRC press; 2004.
• [23]Griffiths TL, Kemp C, Tenenbaum JB: Bayesian models of cognition. In Cambridge handbook of computational cognitive modeling. Edited by Cleeremans A, Dienes Z. New York: Cambridge University Press; 2008:59-100.
• [24]Shiffrin RM, Lee MD, Kim W, Wagenmakers EJ: A survey of model evaluation approaches with a tutorial on hierarchical Bayesian methods. Cognitive Sci 2008, 32:1248-1284.
• [25]Rouder JN, Lu J: An introduction to Bayesian hierarchical models with an application in the theory of signal detection. Psychon B Rev 2005, 12:573-604.
• [26]MacKay DJC: Information theory, inference, and learning algorithms. Cambridge, UK: Cambridge University Press; 2003.
• [27]Robert CP, Casella G: Monte Carlo statistical methods. New York: Springer-Verlag; 1999.
• [28]Podlesnik CA, Sanabria F: Repeated extinction and reversal learning of an approach response supports an arousal-mediated learning model. Behav Process 2011, 87:125-134.
• [29]Killeen PR: Mathematical Principles of Reinforcement. Behav Brain Sc 1994, 17:105-172.
• [30]Bindra D: How adaptive behavior is produced: a perceptual-motivational alternative to response reinforcements. Behav Brain Sc 1978, 1:41-52.
• [31]Bouton ME: Context and behavioral processes in extinction. Learn Memory 2004, 11:485-494.
• [32]Rescorla R: Inhibitory associations between S and R in extinction. Learn Behav 1993, 21:327-336.
• [33]Lattal KM, Lattal KA: Facets of Pavlovian and operant extinction. Behav Process 2012, 90:1-8.
• [34]Johansen EB, Sagvolden T: Response disinhibition may be explained as an extinction deficit in an animal model of attention-deficit/hyperactivity disorder (ADHD). Behav Brain Res 2004, 149:183-196.
• [35]Johansen EB, Sagvolden T: Slower extinction of responses maintained by intra-cranial self-stimulation (ICSS) in an animal model of attention-deficit/hyperactivity disorder (ADHD). Behav Brain Res 2005, 162:22-31.
• [36]Reed P: An experimental analysis of steady-state response rate components on variable ratio and variable interval schedules of reinforcement. J Exp Psychol Anim B 2011, 37:1-9.
• [37]Johnson JE, Pesek EF, Newland MC: High-rate operant behavior in two mouse strains: a response-bout analysis. Behav Process 2009, 81:309-315.
• [38]Conover KL, Fulton S, Shizgal P: Operant tempo varies with reinforcement rate: implications for measurement of reward efficacy. Behav Process 2001, 56:85-101.
• [39]Shull RL: Bouts of responding on variable-interval schedules: effects of deprivation level. J Exp Anal Behav 2004, 81:155.
• [40]Killeen PR: The First Principle of Reinforcement. In Models of action: Mechanisms for adaptive behavior. Edited by Wynne CDL, Staddon JER. Hillsdale: Lawrence Erlbaum; 1998:127.
• [41]Ross RT, Holland PC: Conditioning of simultaneous and serial feature-positive discriminations. Learn Behav 1981, 9:293-303.
• [42]Shull RL, Grimes JA: Bouts of responding from variable-interval reinforcement of lever pressing by rats. J Exp Anal Behav 2003, 80:159.
• [43]Meneses A, Castillo C, Ibarra M, Hong E: Effects of aging and hypertension on learning, memory, and activity in rats. Physiol Behav 1996, 60:341-345.
• [44]Kollins SH, Lane SD, Shapiro SK: Experimental analysis of childhood psychopathology: A laboratory matching analysis of the behavior of children diagnosed with attention-deficit hyperactivity disorder (ADHD). Psychol Rec 1997, 47:25-44.
• [45]Sanabria F, Killeen PR: Evidence for impulsivity in the Spontaneously Hypertensive Rat drawn from complementary response-withholding tasks. Behav Brain Funct 2008, 4:7. BioMed Central Full Text