Conservation of behavioural topography to dopamine D1-like receptor agonists in mutant mice lacking the D1A receptor implicates a D1-like receptor not coupled to adenylyl cyclase

Dopamine D1 vs D5 receptor-dependent induction of seizures in relation to DARPP-32, ERK1/2 and GluR1-AMPA signalling

“…This finding supports our recent observation that SKF 83822-induced behavioral seizures are conserved in D 5 receptor knockouts and, together with numerous reports that the PLC-stimulating SKF 83959 does not induce seizures (Clifford et al, 1999;McNamara et al, 2003;O'Sullivan et al, 2005O'Sullivan et al, , 2006, provides strong evidence that the ability of certain D 1 -like agonists to lower seizure threshold (DeNinno et al, 1991;Starr and Starr, 1993) is critically dependent on selective D 1 receptor stimulation of AC-mediated signalling transduction cascades. Unlike other selective D 1 -like agonists, SKF 83822 induced mildly stereotyped sniffing, locomotion and rearing directed around the perimeter of the cage (thigmotaxis) in wild-type but not D 1 knockouts.…”

“…Secondly, multiple intracellular signal transduction coupling at each receptor serves to increase their functional diversity (O'Sullivan et al, 2004). The availability and detailed characterisation of D 1 and D 5 receptor knockouts has increased our understanding of the gross functional roles of these receptors (Clifford et al, 1998(Clifford et al, , 1999 , 2005, 2006). A significant dose × genotype interaction for overall levels of grooming at higher doses most likely reflects moderate inhibition of grooming in control animals with the emergence of prominent seizures, rather than a dose-dependent release of this behavior in D 1 knockouts per se.…”

Comparative, Topographically-Based Evaluation of Behavioural Phenotype and Specification of D1-Like:D2 Interactions in a Line of Incipient Congenic Mice with D2 Dopamine Receptor 'Knockout'

“…Assessments were carried out using a rapid time-sampling behavioural checklist technique, in a manner similar to that described previously (Clifford et al , 1999.…”

“…Indeed, the studies of Kelly et al (1998) suggest a material contribution from differences in genetic background to the diversity of findings between laboratories in relation to the behavioural phenotype of D 2 knockout. Recently, we have examined the initial cohort of D 2 knockouts constructed by Baik et al (1995) using an approach that is ethologically-based in relation to strains of laboratory mice bred and housed over multiple generations under such conditions; this approach resolves all topographies of behaviour within the mouse repertoire and has been applied by us previously to define the ethogram of D 1A knockouts and to identify novel phenotypic features in terms of the 'sculpting' of behavioural topography over habituation from active exploration through to quiescence (Clifford et al , 1999. The phenotype for the D 2 knockout line of Baik et al (1995) was characterised over initial exploration by modest but significant reductions in locomotion, grooming, rearing free and rearing to wall; rearing seated, sniffing, sifting and stillness were not altered.…”

“…Furthermore, we have contrasted spontaneous behavioural topography with responsivity to the well-established selective D 2 -like agonist RU 24213 (Euvrard et al 1980;Claudi et al 1994;Waddington et al 1995;Clifford et al 1999) and applied the selective D 1 -like agonist A 68930 (DeNinno et al 1991;Daly and Waddington 1993;Waddington et al 1995: Clifford et al 1999) to probe for additional phenotypic effects at the level of D 1 -like: D 2 -like interactions.…”