Effects of a Dopamine D3 Receptor Ligand, BP 897, on Acquisition and Expression of Food-, Morphine-, and Cocaine-induced Conditioned Place Preference, and Food-seeking Behavior in Rats

Abstract

The present study addressed the role of dopaminergic D 3 receptors (D 3 R) in motivational processes in rats. The effects of the selective D 3 R partial agonist, BP 897 (0.25-1 mg/kg, i.p.), on the establishment and the expression of conditioned place preference (CPP) supported by food, morphine (4 mg/kg, s.c.), or cocaine (2 mg/kg, s.c.) were investigated using an unbiased, one-compartment, placeconditioning procedure. When administered alone, BP 897 (0.05-2 mg/kg, i.p.) did not support CPP; on the contrary, conditioned place avoidance (CPA) was observed at 1 mg/kg, suggesting that this dose of BP 897 could be perceived as aversive. When given before each cocaine injection during the conditioning phase, BP 897 (1 mg/kg) prevented the establishment of CPP, and a single administration of BP 897 (0.5 and 1 mg/kg) before the test session impaired the expression of cocaine CPP. In contrast, neither the establishment nor the expression of food-and morphine-CPP were significantly altered by BP 897 (up to 1 mg/kg), whereas the full but less selective D 3 /D 2 R agonists, 7-OH-DPAT (0.5-2 mg/kg, s.c.) and quinelorane (1 mg/kg, s.c.), prevented the acquisition of food CPP. In a within-session extinction schedule of lever pressing for food, BP 897 (0.06-2 mg/kg) was ineffective in potentiating response reinstatement induced by the noncontingent delivery of two food pellets, in contrast with quinelorane and 7-OH-DPAT where previous studies showed to be efficient in this respect (Duarte et al, 2003). These results indicate that BP 897 has no positive appetitive value on its own, and that a moderate degree of stimulation of D 3 R is not sufficient to modulate food-primed food-seeking behavior or alter incentive motivation for food, morphine, and/or their associated cues. However, D 3 R are likely involved in the perception of the rewarding value of cocaine and cocaine-paired cues. This suggests that the appetitive effects of cocaine are subserved by mechanisms different, at least in part, from those of morphine and food, and that D 3 R play a role only in the former.

The selective dopamine D3 receptor antagonists SB-277011A and NGB 2904 and the putative partial D3 receptor agonist BP-897 attenuate methamphetamine-enhanced brain stimulation reward in rats

“…This is consistent with previous studies demonstrating that haloperidol (a preferential D 2 vs D 3 receptor antagonist) and raclopride (a mixed D 2 /D 3 receptor antagonist) have dysphorigenic or aversive properties in both humans and laboratory animals (Singh et al 1996;Kita et al 1999;Baldo et al 1999; see review by Platt et al 2002). This is also consistent with previous studies demonstrating that BP-897 produces an aversive-like effect, as assessed in the BSR and conditioned place preference/aversion paradigms (Duarte et al 2003;Gyertyán and Gál 2003;Campos et al 2004). In addition, BP-897 also produces a compensatory increase in cocaine self-administration (Gyertyán and Gál 2003), and inhibits quinpirole (a mixed D 2 / D 3 receptor agonist)-induced inhibition of DA neuronal firing in the substantia nigra, similar to the D 2 receptor antagonist haloperidol (Wicke and Garcia-Ladona 2001).…”

Mice with Chronically Elevated Dopamine Exhibit Enhanced Motivation, but not Learning, for a Food Reward

“…Disruption of dopamine function by administration of dopamine receptor antagonists impairs Pavlovian conditioning (Di Ciano et al, 2001;Duarte et al, 2003;Parkinson et al, 2002;Spyraki et al, 1982). However, in the current study, both DAT KD and WT mice acquired anticipatory responses to the cue light that was associated with the food at similar rates.…”

“…Disruption of dopamine function by administration of dopamine receptor antagonists impairs acquisition of food conditioned place preference (Duarte et al, 2003;Spyraki et al, 1982), Pavlovian approach behavior (Di Ciano et al, 2001;Parkinson et al, 2002), and lever pressing for a food reward (Smith-Roe and Kelley, 2000;Wise and Schwartz, 1981). Moreover, it has been shown that dopamine neuron firing correlates with reward-related learning (Roitman et al, 2004;Schultz, 2002) perhaps by modulating synaptic plasticity (Calabresi et al, 1992;Centonze et al, 2001).…”

The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

“…BP-897 significantly decreases the discriminative stimulus effects of D-amphetamine and cocaine [21] and attenuates the expression and acquisition of the CPP response to cocaine without altering the acquisition or expression of the CPP response to food or morphine [88]. However, BP-897 alone produced CPA, a finding congruent with that of Gyertyán and Gál [121], and may also have anxiolytic properties [246].…”