- The ventral tegmental area (VTA) and the basolateral amygdala (BLA) have long been regarded as key components in the brain reward circuit.
- Chronic opiate administration switches the functional role of intra-BLA dopamine (DA) transmission from a D1-dependent substrate to a D2-dependent substrates.
- This D1/D2 opiate reward switch in the BLA can directly modulate opiate reward information from the VTA. Furthermore, the DA reward processing occurs in the nucleus accumbens shell (not core)
Author Abstract (Lintas, et. al) : Transmission through dopamine D1 versus D2 receptors in the basolateral amygdala represents an opiate addiction switching mechanism controlling opiate memory encoding in the drug naïve versus dependent state
The basolateral nucleus of the amygdala (BLA) receives innervation from dopaminergic fibers, and dopamine (DA) D1 and D2 receptors are expressed in this region. BLA sends excitatory afferents to the nucleus accumbens (NAcc), to both shell and core regions. The NAcore and NAshell are both implicated in the processing of various associative reward stimuli. However, the precise role of D1 versus D2 receptor transmission in the processing of associative, opiate-related reward learning is not presently understood. Using a combination of in vivo single unit extracellular recording in the NAcc combined with behavioural pharmacology studies, we have identified a double dissociation in the functional role of DA D1 versus D2 receptor transmission in the BLA, as a function of opiate exposure state: thus, in previously opiate-naïve rats, blockade of intra-BLA D1, but not D2, receptor transmission blocks the rewarding effects of morphine (5mg/kg;i.p.) measured in an unbiased conditioned place preference (CPP) procedure. In direct contrast, in rats made opiate dependent and in a state of withdrawal, intra-BLA D2, but not D1 receptor blockade completely blocks opiate reward encoding. We find the same double dissociation with intra-BLA D1/D2 activation: in opiate-naïve rats, pharmacological activation of intra-BLA D1 (but not D2) receptors strongly potentiates sub-threshold morphine (0.05mg/kg;i.p.) reward encoding while activation of D2 receptors (but not D1 receptors) potentiates sub-threshold morphine reward transmission in opiate dependent/withdrawn rats. Single unit recordings performed in neurons of the NAcc shell (but not core) confirm the modulatory role of BLA D1/D2 transmission in NAcc neuronal responses to morphine (1mg/kg;i.v.). Thus, blockade of intra-BLA D1 (but not D2) transmission blocks NAcc neuronal responding to morphine in opiate naïve rats, while blockade of BLA D2 (but not D1) receptors blocks neuronal responding to morphine in opiate dependent/withdrawn rats. Our results characterize and identify a novel and unique opiate addiction switching mechanism directly in the BLA, that can control the encoding of opiate reward information (behaviourally and neuronally) as a direct function of opiate exposure state, via D1 or D2 receptor signalling.