Dopamine D3 Receptors in the Basolateral Amygdala and the Lateral Habenula Modulate Cue-Induced Reinstatement of Nicotine Seeking

Khaled, Maram; Pushparaj, Abhiram; Ciano, Patricia Di; Díaz, Jorge; Foll, Bernard Le

doi:10.1038/npp.2014.158

Cited by 50 publications

(35 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results are in line with studies using second-order schedules of reinforcement which have consistently shown SB-277011A does not impair responding when food is used as the US [34]. There are, however, a number of studies supporting a role for D 3 in responding to drug-associated cues [55–58]. Thus, the effects of a specific D 3 antagonist on sign-tracking behavior in response to a drug-associated cue might be more reminiscent of the D 2 /D 3 effects shown here.…”

Section: Discussionsupporting

confidence: 87%

Examining the role of dopamine D2 and D3 receptors in Pavlovian conditioned approach behaviors

Fraser

Haight

Gardner

et al. 2016

Behavioural Brain Research

View full text Add to dashboard Cite

Elucidating the neurobiological mechanisms underlying individual differences in the extent to which reward cues acquire the ability to act as incentive stimuli may contribute to the development of successful treatments for addiction and related disorders. We used the sign-tracker/goal-tracker animal model to examine the role of dopamine D2 and D3 receptors in the propensity to attribute incentive salience to reward cues. Following Pavlovian training, wherein a discrete lever-cue was paired with food reward, rats were classified as sign- or goal-trackers based on the resultant conditioned response. We examined the effects of D2/D3 agonists, 7-OH-DPAT (0.01–0.32 mg/kg) or pramipexole (0.032–0.32 mg/kg), the D2/D3 antagonist raclopride (0.1 mg/kg), and the selective D3 antagonist, SB-277011A (6 or 24 mg/kg), on the expression of sign- and goal-tracking conditioned responses. The lever-cue acquired predictive value and elicited a conditioned response for sign- and goal-trackers, but only for sign-trackers did it also acquire incentive value. Following administration of either 7-OH-DPAT, pramipexole, or raclopride, the performance of the previously acquired conditioned response was attenuated for both sign- and goal-trackers. For sign-trackers, the D2/D3 agonist, 7-OH-DPAT, also attenuated the conditioned reinforcing properties of the lever-cue. The selective D3 antagonist did not affect either conditioned response. Alterations in D2/D3 receptor signaling, but not D3 signaling alone, transiently attenuate a previously acquired Pavlovian conditioned response, regardless of whether the response is a result of incentive motivational processes. These findings suggest activity at the dopamine D2 receptor is critical for a reward cue to maintain either its incentive or predictive qualities.

show abstract

Section: Discussionsupporting

confidence: 87%

Examining the role of dopamine D2 and D3 receptors in Pavlovian conditioned approach behaviors

Fraser

Haight

Gardner

et al. 2016

Behavioural Brain Research

View full text Add to dashboard Cite

show abstract

“…The importance of the BLA in conditioned reinforcement was further exemplified in a study which found that infusion of SB-277011-A into the BLA reduced cue-induced reinstatement of nicotine-seeking (Khaled et al, 2014). A selectivity of effects was demonstrated in that infusion of SB-277011-A into the BLA had no effect on responding for food.…”

Section: Intra-cerebral Studies Of the Effects Of D3 Agents On Drug-smentioning

confidence: 99%

“…An interesting finding of the Khaled et al (2014) study is the demonstration that infusion of SB-277011-A into the lateral habenula (LHb) decreased cue-induced reinstatement of nicotine-seeking (Khaled et al, 2014). This is the first study of the role of D3 receptors, or the LHb, on conditioned reinforcement.…”

Section: Intra-cerebral Studies Of the Effects Of D3 Agents On Drug-smentioning

confidence: 99%

“…Belonging to the D2-family, the D3 receptor is about 50% homologous with the D2 receptor (Sibley and Monsma, 1992). As compared to the D2 receptor, its restricted localization to limbic areas (Bouthenet et al, 1991; Gurevich and Joyce, 1999; Khaled et al, 2014) suggests that the D3 receptor may be uniquely involved in aspects such as motivation, emotion and learning. In particular, a great deal of interest has emerged in targeting D3 receptors, as distinct from the D2 receptors, for the treatment of drug addiction (Heidbreder, 2005), and in particular, focus has been on the development of selective D3 antagonists and partial agonists (Di Ciano et al, 2003; Pilla et al, 1999; Vorel et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neuronal circuitry underlying the impact of D3 receptor ligands in drug addiction

Foll

Ciano

2015

European Neuropsychopharmacology

Self Cite

View full text Add to dashboard Cite

Since the cloning of the D3 receptor in the early 1990s, there has been a great deal of interest in this receptor as a possible therapeutic target for drug addiction. The development of a D3 ligand suitable for use in humans has remained elusive, so the study of the function of the D3 receptor and its possible therapeutic efficacy has largely been restricted to animals. Pre-clinical studies have established that systemic administration of D3 ligands, particularly antagonists and partial agonists, can alter drug-seeking in animals. Despite over a decade of research, few studies have investigated the effects of intra-cerebral infusion of D3 ligands on drug-seeking. In the present review, we summarize these studies, which have largely focused on stimulus-controlled behaviors. Converging evidence from studies of D3 receptor expression, Fos and phMRI is also provided to delineate some of the D3 brain systems involved in drug-seeking and taking. The data so far indicate that different brain systems may be involved in different types of stimulus control as well as drug taking.

show abstract

“…Stress-induced reinstatement of nicotine-seeking behavior is attenuated by activation of α2 adrenergic receptors in the CeA [143]. Similarly, blockade of dopamine D3 receptors in the BLA attenuates cue-induced reinstatement of nicotine seeking [248]. These findings suggest that CeA α2 adrenergic receptors and BLA dopamine D3 receptors differentially mediate reinstatement of nicotine seeking elicited by stress and cues.…”

Section: Neurophysiological Mechanisms Underlying Nicotine-seeking Bementioning

confidence: 89%

Neurobiological and Neurophysiological Mechanisms Underlying Nicotine Seeking and Smoking Relapse

2018

View full text Add to dashboard Cite

Tobacco-related morbidity and mortality continue to be a significant public health concern. Unfortunately, current FDA-approved smoking cessation pharmacotherapies have limited efficacy and are associated with high rates of relapse. Therefore, a better understanding of the neurobiological and neurophysiological mechanisms that promote smoking relapse is needed to develop novel smoking cessation medications. Here, we review preclinical studies focused on identifying the neurotransmitter and neuromodulator systems that mediate nicotine relapse, often modeled in laboratory animals using the reinstatement paradigm, as well as the plasticity-dependent neurophysiological mechanisms that facilitate nicotine reinstatement. Particular emphasis is placed on how these neuroadaptations relate to smoking relapse in humans. We also highlight a number of important gaps in our understanding of the neural mechanisms underlying nicotine reinstatement and critical future directions, which may lead toward the development of novel, target pharmacotherapies for smoking cessation.

show abstract

Dopamine D3 Receptors in the Basolateral Amygdala and the Lateral Habenula Modulate Cue-Induced Reinstatement of Nicotine Seeking

Cited by 50 publications

References 51 publications

Examining the role of dopamine D2 and D3 receptors in Pavlovian conditioned approach behaviors

Examining the role of dopamine D2 and D3 receptors in Pavlovian conditioned approach behaviors

Neuronal circuitry underlying the impact of D3 receptor ligands in drug addiction

Neurobiological and Neurophysiological Mechanisms Underlying Nicotine Seeking and Smoking Relapse

Contact Info

Product

Resources

About