Electron microscopic dual labeling of high‐affinity neurotensin and dopamine D2 receptors in the rat nucleus accumbens shell

Abstract

The dopamine D2 receptor (D2R) in the nucleus accumbens (NAc) shell is implicated in schizophrenia and in psychostimulant-induced drug-seeking behavior, both of which are affected by activation of the functionally opposed high-affinity neurotensin receptor (NTS1). To determine the functionally relevant sites, we examined the dual electron microscopic immunocytochemical localization of D2R and NTS1 in the NAc shell of rat brain. Immunolabeling for each receptor was seen in association with cytoplasmic organelles, or more rarely, on the plasma membrane of both axonal and somatodendritic profiles. Some of the axonal and many of the dendritic processes colocalized the two receptors. The dually labeled axon terminals often formed symmetric synapses or appositional contacts with unlabeled dendritic profiles. The morphology of these terminals suggests that they contain either inhibitory amino acids or dopamine. Other axonal profiles expressing exclusively NTS1 or D2R were without synaptic specializations or formed asymmetric, excitatory-type synapses mainly on unlabeled dendritic spines. In addition, however, several D2R-immunoreactive terminals were observed presynaptic to dendrites containing NTS1. The somatodendritic profiles immunolabeled for NTS1 and/or D2R had morphological features typical of inhibitory spiny projection neurons in the NAc. These results suggest that activation of NTS1 and D2R can dually modulate transmitter release from the same or separate phenotypically distinct axon terminals in the NAc shell. These presynaptic receptors as well as the postsynaptic NTS1 distribution in neurons that also contain or receive input from terminals containing D2R may mediate the opposing actions of neurotensin and dopamine in the NAc.

Ketamine Induces Dopamine-Dependent Depression of Evoked Hippocampal Activity in the Nucleus Accumbens in Freely Moving Rats

“…These findings are consistent with reports that activation of D 2 receptors can depress neurotransmission at excitatory synapses in the NAc, thought to be mediated by a presynaptic mechanism of action (Yang and Mogenson, 1986;O'Donnell and Grace, 1994;Brady and O'Donnell, 2004). In support of this, a recent electron microscopy study has confirmed the existence of D 2 receptors at excitatory terminals in the NAc (Delle Donne et al, 2004). However, the role of DA in the NAc is complex and DA-mediated depression of excitatory neurotransmission can also occur by a mechanism involving D 1 receptors (Pennartz et al, 1992;Harvey and Lacey, 1996;Nicola et al, 1996Nicola et al, , 2000.…”

Neurotensin Receptor 1 Gene Polymorphisms Are Associated with Personality Traits in Healthy Chinese Individuals

“…Radioimmunoassay results of animals and men showed that NT was present in all mammalian brain structures containing dopamine nerve cell bodies and terminals such as the substantia nigra, the ventral tegmental area, the striatum, the nucleus accumbens, and the prefrontal cortex [25,32]. Moreover, NTR1 was localized both presynaptically and postsynaptically at dopaminergic synapses expressing DRD2 in the striatum, nucleus accumbens, and ventral midbrain [33]. The anatomical overlap between NT, NTR1, dopamine, and DRD2 could allow for extensive functional interactions at the cellular level.…”

Dendritic distributions of dopamine D1 receptors in the rat nucleus accumbens are synergistically affected by startle-evoking auditory stimulation and apomorphine

“…Furthermore, D1R activation in the striatum facilitates sensorimotor cortical functions (Steiner and Kitai, 2000). Unlike D2Rs, D1Rs are predominantly located in distal dendrites and dendritic spines, which are major sites for synaptic plasticity (Delle Donne et al, 2004;Hara and Pickel, 2005). The surface expression of D1R is not stationary, but dynamically changed by synaptic activity and the availability of D1R agonists (Dumartin et al, 1998;Lamey et al, 2002).…”