Psychopharmacological Distinction Between Novel Full-Efficacy “D1-like” Dopamine Receptor Agonists

Deveney, A. M.; Waddington, John L.

doi:10.1016/s0091-3057(97)00248-7

Cited by 26 publications

(17 citation statements)

References 36 publications

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“…In previous studies, dopamine D1 agonists were needed to cause sequential super-stereotypy of syntactic grooming chains, whereas D2 agonists in contrast reduced initiation and completion of syntactic grooming chains (even though D2 agonists can cause simple repetitive movement stereotypies) [43-45,64]. Future studies will be needed to confirm whether the sequential super-stereotypy of DAT knockdown mutant mice depends specifically on increased D1 receptor activation.…”

Section: Discussionmentioning

confidence: 98%

“…Enhanced sequential stereotypy would be reflected if the complex serial pattern as a whole entity became more sequentially rigid or persistent. Indeed, in rats, pharmacological boosting by dopamine D1 agonists administered systemically or into brain ventricles produces sequential super-stereotypy of syntactic grooming chains [43-45]. In a state of sequential super-stereotypy, the stereotyped pattern becomes even more predictable than normal, which is evident as an increase in the probability that all four phases will be completed in syntactic order [43,44].…”

Section: Introductionmentioning

confidence: 99%

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et al. 2005

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Background: Excessive sequential stereotypy of behavioral patterns (sequential super-stereotypy) in Tourette's syndrome and obsessive compulsive disorder (OCD) is thought to involve dysfunction in nigrostriatal dopamine systems. In sequential super-stereotypy, patients become trapped in overly rigid sequential patterns of action, language, or thought. Some instinctive behavioral patterns of animals, such as the syntactic grooming chain pattern of rodents, have sufficiently complex and stereotyped serial structure to detect potential production of overlyrigid sequential patterns. A syntactic grooming chain is a fixed action pattern that serially links up to 25 grooming movements into 4 predictable phases that follow 1 syntactic rule. New mutant mouse models allow gene-based manipulation of brain function relevant to sequential patterns, but no current animal model of spontaneous OCDlike behaviors has so far been reported to exhibit sequential super-stereotypy in the sense of a whole complex serial pattern that becomes stronger and excessively rigid. Here we used a hyper-dopaminergic mutant mouse to examine whether an OCD-like behavioral sequence in animals shows sequential super-stereotypy. Knockdown mutation of the dopamine transporter gene (DAT) causes extracellular dopamine levels in the neostriatum of these adult mutant mice to rise to 170% of wild-type control levels.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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et al. 2005

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“…Using behavioural techniques very similar to those employed here, we have reported the generic D 2 -like agonist RU 24213 to induce sni¦ng, locomotion and chewing but with little rearing ; conversely, the D 3 -preferring agonists 7-OH-DPAT and quinelorane can at higher (non-selective?) doses induce sni¦ng and chewing with some locomotion but not rearing (Murray and Waddington 1989;Daly and Waddington 1993a), while the generic D 1 -like agonist A 68930 induces grooming, vacuous chewing, sni¦ng, chewing and rearing but not locomotion (Daly and Waddington 1993b;Deveney and Waddington 1997). On this basis, the ethogram of U99194A is more similar to, though not identical with, that of the D 2 -like agonist.…”

Section: E¤ects Of Haloperidol On Behavioural Responses To U99194amentioning

confidence: 90%

Heterogeneity of behavioural profile between three new putative selective D 3 dopamine receptor antagonists using an ethologically based approach

Clifford¹,

Waddington²

1998

Psychopharmacology

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The effects on behaviour of the putative selective D3 dopamine receptor antagonists GR 103691, nafadotride and U 99194A were compared with those of the generic D2-like antagonist haloperidol, using an ethologically based approach. Neither GR 103691 (0.008-1.0 mg/kg) nor nafadotride (0.025-1.6 mg/kg) influenced any element of behaviour. Conversely, U99194A (1.67-45 mg/kg) effected a dose-dependent stimulation of episodes of non-stereotyped sniffing, locomotion, chewing and eating, with some stimulation of rearing, and reduced baseline levels of grooming; thereafter, as sniffing and locomotion declined, stimulation of episodes of grooming emerged. Haloperidol (0.0008-0.1 mg/kg) failed to promote any element of behaviour and reduced baseline levels of grooming; responsivity to U99194A was antagonised by pretreatment with haloperidol. The lack of effect of GR 103691 (> 100-fold D3/D2 selectivity) and nafadotride (10-fold D3/D2 preference), in contrast to the characteristic "ethogram" for U99194A (25-fold D3/D2 selectivity), indicated a fundamental difference in their mechanisms of action. This topography of responsivity to U99194A overlapped somewhat with the profiles of both D2-like and D1-like agonists, and its sensitivity to antagonism by haloperidol also indicated a dopaminergic basis thereto. However, differences among GR 103691, nafadotride and U99194A bore no relation to their relative selectivities for the D3 receptor, and the basis thereof remains unclear. Theorising as to the behavioural role of the D3 receptor may need to be tempered pending the identification of a range of chemically distinct D3 antagonists of higher selectivity.

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“…Dopamine agonists and antagonists also modulate the strength of instinctive chains of 25 or so grooming movements that all rodents show, apparently by acting on dorsolateral striatum Cromwell and Berridge 1996;Deveney and Waddington 1997). Those action patterns are not only nonlearned, they are also centrally patterned by brain systems rather than being guided by S-R chains of responses to discrete stimuli.…”

Section: Habit Learning?mentioning

confidence: 99%