Modulation of Dopamine Receptor Agonist-Induced Rotational Behavior in 6-OHDA-Lesioned Rats by a Peptidomimetic Analogue of Pro-Leu-Gly-NH2 (PLG)

Effects of the Dopamine D2 Allosteric Modulator, PAOPA, on the Expression of GRK2, Arrestin-3, ERK1/2, and on Receptor Internalization

“…PAOPA also has no statistically significant effect on specific binding of D2 antagonists such as [ 3 H]-spiperone [24]. Additionally, in animal models (e.g., 6-hydropdopamine (6-OHDA); vacuous chewing movement models) PAOPA has shown to potentiate the activity of D2 agonists, such as apomorphine [57,58], and attenuate the effects of D2-specific antagonist haloperidol [58]. Finally, the increases in the expression of GRK2, arrestin-3 and ERK1/2 observed in this study were seen to occur within the striatum of PAOPA-treated rats.…”

PAOPA, a potent analogue of Pro-Leu-glycinamide and allosteric modulator of the dopamine D2 receptor, prevents NMDA receptor antagonist (MK-801)-induced deficits in social interaction in the rat: Implications for the treatment of negative symptoms in schizophrenia

“…Previous research from our lab has demonstrated that the endogenous brain tripeptide PLG and its analog PAOPA (Figure 1) modify dopaminergic neurotransmission by acting as allosteric modulators of the DA D 2 receptor (Johnson et al 1986;Mishra 1983;Mishra et al 1983;Mishra et al 1997;Verma et al 2005;Chiu et al 1981;Chiu et al 1983;Raghavan et al 2009;Srivastava et al 1988;Verma et al 2005). These compounds have been shown to increase agonist binding to DA D 2 receptors without affecting antagonist binding, and prevent conversion of high-affinity state DA receptors (D 2 High ) to their low-affinity state (D 2 Low ) (Mishra et al 1990;Srivastava et al 1988;Verma et al 2005).…”

“…These compounds have been shown to increase agonist binding to DA D 2 receptors without affecting antagonist binding, and prevent conversion of high-affinity state DA receptors (D 2 High ) to their low-affinity state (D 2 Low ) (Mishra et al 1990;Srivastava et al 1988;Verma et al 2005). Furthermore, PLG and PAOPA have been shown to potentiate rotational behaviour in the 6-hydroxy dopamine lesion rat (Mishra et al 1997;Ott et al 1996;Smith and Morgan 1982), and inhibit neuroleptic drug-induced vacuous chewing in rat models of human tardive dyskinesia (Castellano et al 2007;Sharma et al 2003). Given the interaction between PAOPA and the DA D 2 receptor, and the effects of PAOPA in preclinical animal models, the objective of this study was to investigate whether this potent analog of PLG has an effect on MK-801-induced social withdrawal in the rat.…”

Change in expression of vesicular protein synapsin II by chronic treatment with D2 allosteric modulator PAOPA

“…Previous in vitro and in vivo studies with PAOPA have shown its specificity in modulating D2 and D4 receptors, with no significant effects occurring at D1 or D3 receptors, or the ␣2-adrenergic receptor [48]. Additionally, within in vivo models, PAOPA can potentiate the effect of D2 agonists, such as apomorphine [6,37], and attenuate effects of the D2-specific antagonist, haloperidol [6]. These interactions have been shown to occur through an allosteric interaction with D2R, as PAOPA does not compete with radioligands binding to the D2 orthosteric site [34].…”