The morphogenesis of stereotyped behavior induced by the dopamine receptor agonist apomorphine in the laboratory rat

Szechtman, Henry; Ornstein, Kurt; Teitelbaùm, Philip; Golani, Ilan

doi:10.1016/0306-4522(85)90143-5

Cited by 113 publications

(36 citation statements)

References 29 publications

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“…Contralateral and ipsiIateral turnings (defined as complete 360° turns) were counted visually by a trained observer who had no prior knowledge of the drug treatment. Description of the stepping pattern involved analysis of the presence/absence of the following items: (1) lateral head movements, defined as lateral movements of the head in relation to the upper torso; (2) lateral torso movements, defined as lateral movements of the upper torso in relation to the lower torso; (3) lateral pelvic movements, defined as lateral movements of the lower torso in relation to the hindquarters; (4) normal hindiimb stepping during turning, characterized by the sequential occurrence of two forward steps (hindiimb forward steps: Cools and Jongen-Relo, 1991); (5) (Szechtman et al, 1985); (9) uncou pling of lateral movements of the torso and the limbs, causing the legs to lag behind (dragging). Observations w ere m ade during consecutive 5-min periods for 90-120 min, starting immediately after the injection.…”

Section: Behavioural Methodsmentioning

confidence: 99%

Dissimilarities between cholinergic and dopaminergic turning elicited by nucleus accumbens stimulation in freely moving rats

Saigusa

Koshikawa

Kitamura

et al. 1995

European Journal of Pharmacology

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Contralateral turning was produced by unilateral injection of carbachol (0.5, 2,5, 5 jxg) into the nucleus accumbens, but not into the dorsal or ventral striatum. This behaviour was inhibited by muscarinic Mx acetylcholine receptor blockade in the nucleus accumbens, and less effectively by blockade of muscarinic M2 and nicotinic acetylcholine receptors. Unilateral injection of a mixture of the dopamine Dj receptor agonist l-phenyl-2,3,4,5-tetrahydro-lii-3-benzazepine-7,8-diol (SKF 38393, 5 fig) and the dopamine D 2 receptor agonist quinpirole (10 ¡ig) also produced contralateral turning. The stepping pattern, however, completely differed from that induced by carbachol. The number of carbachol-induced turnings was reduced by dopamine Dz or D2 receptor blockade (8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyKl//-3-benzazepine-7-ol (SCH 23390) and /-sulpiride, respec tively) in the nucleus accumbens. However, the reduction was due to a change in the turning pattern. Blockade of muscarinic acetylcholine receptors in the nucleus accumbens did not change the contralateral turning induced by unilateral injection of dopamine receptor agonists into the nucleus accumbens. The results demonstrate that there is no functional interaction between the cholinergic and dopaminergic substrates involved, although blockade of the dopamine receptors elicited behavioural deficits that competed with the turning elicited by carbachol. The contralateral turning elicited by carbachol injection into the nucleus accumbens requires an intact dopamine activity at the level of dopamine Dj and D2 receptors in the ipsilateral, but not contralateral, ventrolateral striatum.

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Section: Behavioural Methodsmentioning

confidence: 99%

Dissimilarities between cholinergic and dopaminergic turning elicited by nucleus accumbens stimulation in freely moving rats

Saigusa

Koshikawa

Kitamura

et al. 1995

European Journal of Pharmacology

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Section: Multivariate Assessment Of Locomotor Behaviormentioning

confidence: 99%

“…This wide range of applications is based on the fact that unconditioned motor activity probes a variety of behaviors, can be recorded automatically, and can quickly generate an effect profile (Geyer 1990). A variety of different concepts have been applied to the interpretation of aspects of unconditioned motor behavior of rodents in an open field, including arousal, novelty seeking, diversive and inspective exploration, anxiety, stereotypy, and perseveration (Eilam and Golani 1989,Geyer 1990,Geyer et al 1986, Golani et al 1993, Lat 1965, Sanberg et al 1985, Szechtman et al 1985. In an extensive review of the open field test, Walsh and Cummins suggest the open field elicits affective components of behavior such as fear and excitability (Walsh and Cummins 1976).…”

Section: The Complex Conceptual Basis Of Locomotor Behaviormentioning

confidence: 99%

“…The current situation regarding the assessment of hyperactivity in BD individuals is not unlike the state of the art in assessing animal motor behavior forty years ago (Lat 1965). Since that time, several research groups (Eilam and Golani 1989,Szechtman et al 1985 have developed sophisticated approaches to quantify locomotor and exploratory behavior in rodents.The results from these approaches have shown that assessment of motor activity is complex (Eilam and Golani 1989,File and Wardill 1975,Geyer 1990,Geyer and Paulus 1996,Geyer et al 1986,Paulus and Geyer 1996,Szechtman et al 1985 but important for understanding a wide range of phenomena ranging from how drugs affect behavior to the phenotype of genetic mutant mice. We submit in this review that multivariate assessments of both the amounts and sequential patterns of motor actions in humans can potentially provide far greater knowledge on the characteristics of locomotor behavior as well as the effects of treatment compared to existing methods.…”

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confidence: 99%

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A reverse-translational approach to bipolar disorder: Rodent and human studies in the Behavioral Pattern Monitor

Young

Minassian

Paulus

et al. 2007

Neuroscience & Biobehavioral Reviews

106

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Mania is the defining feature of Bipolar Disorder (BD). There has been limited progress in understanding the neurobiological underpinnings of BD mania and developing novel therapeutics, in part due to a paucity of relevant animal models with translational potential. Hyperactivity is a cardinal symptom of mania, traditionally measured in humans using observer-rated scales. Multivariate assessment of unconditioned locomotor behavior using the rat Behavioral Pattern Monitor (BPM) developed in our laboratory has shown that hyperactivity includes complex multifaceted behaviors. The BPM has been used to demonstrate differential effects of drugs on locomotor activity and exploratory behavior in rats. Studies of genetically engineered mice in a mouse BPM have confirmed its utility as a cross-species tool. In a "reverse-translational" approach to this work, we developed the human BPM to characterize motor activity in BD patients. Increased activity, object interactions, and altered locomotor patterns provide multidimensional phenotypes to model in the rodent BPM. This unique approach to modeling BD provides an opportunity to identify the neurobiology underlying BD mania and test novel antimanic agents. KeywordsBipolar Disorder; mania; locomotor activity; exploratory; rat; mouse; Behavioral Pattern Monitor; Open Field; hyperactivity Modeling BD maniaBipolar disorder (BD) is a severe psychiatric disorder that affects approximately 2-7% of the general population (Friedman et al. 2006). Mania is the defining feature of BD although patients can also manifest depressive symptoms. During the manic episodes of BD, patients exhibit impulsive behavior, hypersexuality, pressured speech, flight of ideas, and motor hyperactivity, which have been conceptualized as inhibitory failures of behavior and thought (Goodwin and Jamison 1990). These symptoms profoundly impair and disrupt social, occupational, and family life in individuals with BD (Post et al. 2003). Despite the prevalence of this disorder, surprisingly few studies (Franks et al. 1983,Gooding and Tallent 2001,Murphy et al. 1999, have attempted to develop adequate translational models to elucidate the neurobiology * Correspondence should be sent to: Martin P. Paulus, M.D. Department of Psychiatry, UCSD, La Jolla, California, 92093-9116 Phone: (858) Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeurosci Biobehav Rev. Author manuscript; available in PMC 2008 January 1. Published in final edited form as:Neurosci Biobehav Rev. 2007 ; 31(6): 882-896. NIH-PA Author ManuscriptNIH-PA Author Manu...

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“…Contralateral and ipsilateral turnings (defined as complete 360° turns) were counted visually by a trained observer who had no prior knowledge of the drug treatment. Description of the stepping pattern involved analysis of the presence/absence of the following items: (l) lateral head movements, de fined as lateral movements of the head in relation to the upper torso; (2) lateral torso movements, defined as lateral movements of the upper torso in relation to the lower torso; (3) lateral pelvic movements, defined as lateral movements of the lower torso in relation to the hindquar ters; (4) normal hindlimb stepping during turning, charac terized by the sequential occurrence of two forward steps (hindlimb forward steps: Cools and Jongen-Relo, 1991); (5) apomorphine-induced hindlimb stepping, characterized by the sequential occurrence of a closing and an open step (hindlimb doublet: Cools and Jongen-Relo, 1991); (6) normal forelimb stepping during turning, characterized by the sequential occurrence of a closing and an open step (forelimb doublet: Cools and Jongen-Relo, 1991); (7) dexamphetamine-induced forelimb stepping, characterized by the sequential occurrence of a crossing and an open step (forelimb crossing step: Cools and Jongen-Relo, 1991); (8) pivoting, characterized by turning around one leg (Szechtman et al, 1985); (9) uncoupling of lateral movements of the torso and the limbs, causing the legs to lag behind (dragging). Observations were made during consecutive 3.1.…”

Section: Behavioural Methodsmentioning

confidence: 99%

Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2 receptors in the shell of the nucleus accumbens; turning behaviour

Koshikawa

Kitamura

Kobayashi

et al. 1996

European Journal of Pharmacology

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The goal of this study was to determine whether the dopamine D3 receptor in limbic structures plays a role in the shell-specific and dopamine-dependent display of turning behaviour in rats. When combined with the dopamine receptor agonist (± )-i-phenyl-2,3,4,5-tetrahydro-1 //-3-benzazepine-7,8-diol (SKF-38393, 5 jx g ) , the putative dopamine D3 receptor agonist (±)-7-hydroxy-/V,N-di-n-propyl-2-aminotetralin (7-OH-DPAT, 1, 5 and 10 jJLg) elicited contralateral turning in a dose-dependent manner following unilateral injection into the shell, but not the core, of the nucleus accumbens. The turning pattern displayed was identical to that reported previously after intra-accumbens administration of the cocktail of SKF-38393 and the dopamine D2 receptor agonist quinpirole. The behaviour under study was dose-dependently attenuated by local administration of the dopamine Dj receptor antagonist /?(-h)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1//-3-benzazepi ne (SCH 23390: 10 and 100 ng), the dopamine D2 receptor antagonist domperidone (25 and 50 ng) or the dopamine D2/3 receptor antagonist /-sulpiride (5 and 25 ng). Combined blockade of both dopamine Dj and D2 receptors in the shell with a dose of either antagonist alone that produced just a moderate reduction (10 ng SCH 23390 and 50 ng domperidone) completely antagonized the turning behaviour elicited by the cocktail of SKF-38393 and 7-OH-DPAT. Replacing 7-OH-DPAT by another putative dopamine D3 receptor agonist, 5( + )-(4a/?,10W?)-3,4,4tf,10£~tetrahydro-4-propyl-2tf,5//-[l]benzopyrano [4,[3][4][5][6]907, 10 jxg), in the cocktail did produce no turning behaviour at all. It is concluded that mesolimbic dopamine D3 receptors play no role in the dopamine-dependent and shell-specific turning behaviour: the contribution of 7-OH-DPAT in the cocktail of SKF-38393 and 7-OH-DPAT to the display of turning behaviour is solely due to its ability to activate dopamine D2 receptors,

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The morphogenesis of stereotyped behavior induced by the dopamine receptor agonist apomorphine in the laboratory rat

Cited by 113 publications

References 29 publications

Dissimilarities between cholinergic and dopaminergic turning elicited by nucleus accumbens stimulation in freely moving rats

Dissimilarities between cholinergic and dopaminergic turning elicited by nucleus accumbens stimulation in freely moving rats

A reverse-translational approach to bipolar disorder: Rodent and human studies in the Behavioral Pattern Monitor

Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2 receptors in the shell of the nucleus accumbens; turning behaviour

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