Behavioural pharmacology op ‘D-1-like’ dopamine receptors: Further subtyping, new pharmacological probes and interactions with ‘D-2-like’ receptors

Mapping the Effects of Three Dopamine Agonists with Different Dyskinetogenic Potential and Receptor Selectivity Using Pharmacological Functional Magnetic Resonance Imaging

“…Studies performed in MPTP-lesioned monkeys are to some extent contradictory on this matter, yet most emphasize that D1/D5 agonists induce significant dyskinesia (Blanchet et al, 1996;Pearce et al, 1999;Goulet and Madras, 2000) and the D1/D5 agonist ABT-431 is as potent as levodopa in inducing dyskinesia in patients (Rascol et al, 2001). Remarkably, we found that SKF-81297 induced significantly more MD than apomorphine and quinpirole, what is consistent with reports showing that D1/D5 agonists increase oral movements in rats and monkeys with intact dopaminergic pathways (Bedard and Boucher, 1989;Waddington et al, 1995) and produce abnormal dyskinetic oral movements in MPTP-lesioned marmosets (Gnanalingham et al, 1995). Overall, these findings are well in line with recent research showing altered D1 receptor signaling in the striatum of parkinsonian rats (Gerfen et al, 2002) and MPTP monkeys rendered dyskinetic by chronic levodopa administration (Aubert et al, 2005), and further support the usefulness of rodent models of PD for the study of dopamine agonistinduced dyskinesia.…”

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'

“…Typical D 2 -like-initiated behaviours such as stereotyped sniffing and locomotion are regulated in a co-operative/synergistic manner by tonic or phasic activity through D 1 -like receptors; conversely, atypical behaviours appear to be regulated in an oppositional manner such that vacuous chewing has its genesis in tonic or phasic activity through D 1 -like receptors but is released/enhanced by reduction in DAergic activity through D 2 -like receptors (Waddington et al 1994(Waddington et al , 1995. However, the involvement of individual family members in these effects is poorly understood.…”

“…Members of the D 2 -like dopamine (DA) receptor family [D 2L/S , D 3 , D 4 ] (Bunzow et al 1988;Giros et al 1989;Sokoloff et al 1990;Van Tol et al 1991) constitute a series of proteins that are now recognised to play a fundamental role in the regulation of multiple aspects of mammalian psychomotor behaviour, both as independent entities and through functional interactions with their D 1 -like [D 1A/1 , D 1B/5 ] counterparts (Waddington et al 1995Missale et al 1998). Although there are available both agonist and antagonist ligands which are highly selective for, and hence can discriminate readily between , these D 2 -like vs. D 1 -like receptor families, there are very few ligands which can yet discriminate materially within each of these families; thus, the distinct functions of individual D 2 -like and D 1 -like receptors are understood primarily at a 'family' level only .…”

“…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.…”

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

“…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. Failure of SKF 83822 to induce syntactic intense grooming in a manner characteristic of other selective D 1 -like agonists (Waddington et al, 1995), combined with previous reports that the ability of SKF 83959 to stimulate intense grooming is reduced in both congenic D 1 and D 5 knockouts (McNamara et al, 2003;O'Sullivan et al, 2005), provides additional evidence that D 1 -like receptor coupling to PLC (but not AC) is necessary to induce complex syntactic grooming behavior, possibly via heterooligomerisation with D 2 receptors (O'Sullivan et al, 2004;Rashid et al, 2007).…”