Activation of glucagon ‐like peptide‐1 receptors in the nucleus accumbens attenuates cocaine seeking in rats

Abstract Recent evidence indicates that activation of glucagon‐like peptide‐1 (GLP‐1) receptors reduces cocaine‐mediated behaviors and cocaine‐evoked dopamine release in the nucleus accumbens (NAc). However, no studies have examined the role of NAc GLP‐1 receptors in the reinstatement of cocaine‐seeking behavior, an animal model of relapse. Here, we show that systemic infusion of a behaviorally relevant dose of the GLP‐1 receptor agonist exendin‐4 penetrated the brain and localized with neurons and astrocytes in the NAc. Administration of exendin‐4 directly into the NAc core and shell subregions significantly attenuated cocaine priming‐induced reinstatement of drug‐seeking behavior. These effects were not due to deficits in operant responding or suppression of locomotor activity as intra‐accumbal exendin‐4 administration had no effect on sucrose‐seeking behavior. To determine the effects of GLP‐1 receptor activation on neuronal excitability, exendin‐4 was bath applied to ex vivo NAc slices from cocaine‐experienced and saline‐experienced rats following extinction of cocaine‐taking behavior. Exendin‐4 increased the frequency of action potential firing of NAc core and shell medium spiny neurons in cocaine‐experienced rats while no effect was observed in saline controls. In contrast, exendin‐4 did not affect the frequency or amplitude of spontaneous excitatory postsynaptic currents or alter the paired‐pulse ratios of evoked excitato...
Source: Addiction Biology - Category: Addiction Authors: Tags: Original Article Source Type: research