Approach to reward is a fundamental adaptive behavior, disruption of which is a core symptom of addiction and depression. Nucleus accumbens (NAc) dopamine is required for reward-predictive cues to activate vigorous reward seeking, but the underlying neural mechanism is unknown. Reward-predictive cues elicit both dopamine release in the NAc and excitations and inhibitions in NAc neurons. However...

Pattern completion, the ability to retrieve complete memories initiated by partial cues, is a critical feature of the memory process. However, little is known regarding the molecular and cellular mechanisms underlying this process. To study the role of dopamine in memory recall, we have analyzed dopamine transporter heterozygous knockout mice (DAT(+/-)), and found that while these mice possess ...

Huntington disease has been linked to increased dopaminergic neurotransmission in the striatum, and clinical studies have demonstrated that the associated chorea can be treated with dopamine antagonist or dopamine-depleting drugs. The origin of this hyperdopaminergic status is unknown. Because substantia nigra pars compacta and the ventral tegmental area are the main sources of striatal dopamin...

The mechanisms underlying the effects of psychostimulants in attention deficit hyperactivity disorder (ADHD) are not well understood, but indirect evidence implicates D2 dopamine receptors. Here we dissect the components of dopaminergic neurotransmission in the hyperactive mouse mutant coloboma to identify pre- and postsynaptic elements essential for the effects of amphetamine in these mice. Am...

Prepulse inhibition (PPI) is a measure of sensorimotor gating and an endophenotype of schizophrenia. We have shown previously in rats that estrogen treatment prevents disruption of PPI by the 5-HT(1A)/5-HT(7) receptor agonist 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT). The aim of the present study was to examine the role of dopamine D(1) and D(2) and serotonin 5-HT(1A), 5-HT(2A), and 5-HT(7)...

Synchronous activation of dopamine neurons, for instance upon presentation of an unexpected rewarding stimulus, results in the release of dopamine from both terminals in projection areas and somatodendritic sites within the ventral midbrain. This report describes an inhibitory postsynaptic current (IPSC) that was elicited by dopamine in slices from mouse midbrain. The IPSC was tetrodotoxin sens...

Subtype-selective antagonists of the peripheral-type (CCK-A) and the central-type (CCK-B) cholecystokinin (CCK) receptors were employed to determine the receptor subtype(s) mediating the modulatory actions of CCK on dopamine-induced changes in exploratory activity at three sites in the mesolimbic pathway of the rat. The CCK-A antagonist L-364,718 (10 ng) blocked CCK potentiation of dopamine-ind...

Introduction: R-[C]-SKF 82957 is a high-affinity and potent dopamine D1 receptor agonist radioligand, which gives rise to a brainpenetrant lipophilic metabolite. In this study, we demonstrate that systemic administration of catechol-O-methyl transferase (COMT) inhibitors blocks this metabolic pathway, facilitating the use of R-[C]-SKF 82957 to image the high-affinity state of the dopamine D1 re...

In the retinas of many species of lower vertebrates, retinal photoreceptors and pigment epithelium pigment granules undergo daily movements in response to both diurnal, and in the case of teleost cone photoreceptors, endogenous circadian signals. Typically, these cone movements take place at dawn and at dusk when teleosts are maintained on a cyclic light (LD) regime, and at expected dawn and ex...