Dopamine D2 Receptors in the Paraventricular Thalamus Attenuate Cocaine Locomotor Sensitization.

Alterations in thalamic dopamine (DA) or DA D2 receptors (D2Rs) have been measured in drug addiction and schizophrenia, but the relevance of thalamic D2Rs for behavior is largely unknown. Using in situ hybridization and mice expressing green fluorescent protein (GFP) under the Drd2 promoter, we found that D2R expression within the thalamus is enriched in the paraventricular nucleus (PVT) as well as in more ventral midline thalamic nuclei. Within the PVT, D2Rs are inhibitory as their activation inhibits neuronal action potentials in brain slices. Using Cre-dependent anterograde and retrograde viral tracers, we further determined that PVT neurons are reciprocally interconnected with multiple areas of the limbic system including the amygdala and the nucleus accumbens (NAc). Based on these anatomical findings, we analyzed the role of D2Rs in the PVT in behaviors that are supported by these areas and that also have relevance for schizophrenia and drug addiction. Male and female mice with selective overexpression of D2Rs in the PVT showed attenuated cocaine locomotor sensitization, whereas anxiety levels, fear conditioning, sensorimotor gating, and food-motivated behaviors were not affected. These findings suggest the importance of PVT inhibition by D2Rs in modulating the sensitivity to cocaine, a finding that may have novel implications for human drug use.

Enhanced left-finger deftness following dominant upper- and lower-limb amputation.

BACKGROUND: After amputation, the sensorimotor cortex reorganizes, and these alterations might influence motor functions of the remaining extremities. OBJECTIVE: The authors examined how amputation of the dominant or nondominant upper or lower extremity alters deftness in the intact limbs. METHODS: The participants were 32 unilateral upper- or lower-extremity amputees and 6 controls. Upper-extremity deftness was tested by coin rotation (finger deftness) and pegboard (arm, hand, and finger deftness) tasks. RESULTS: Following right-upper- or right-lower-extremity amputation, the left hand's finger movements were defter than the left-hand fingers of controls. In contrast, with left-upper- or left-lower-extremity amputation, the right hand's finger performance was the same as that of the controls. CONCLUSIONS: Although this improvement might be related to increased use (practice), the finding that right-lower-extremity amputation also improved the left hand's finger deftness suggests an alternative mechanism. Perhaps in right-handed persons the left motor cortex inhibits the right side of the body more than the right motor cortex inhibits the left side, and the physiological changes induced by right-sided amputation reduced this inhibition.

Normalization of horizontal pseudoneglect following right, but not left, upper limb amputation.

OBJECTIVES: Subjects who have suffered limb amputations are known to have physiological alterations of their body's representation, or schema. Such changes of brain function might alter the right-left spatial allocation of attention. The goal of this study was to learn if, compared to normal subjects, limb amputees had alterations of right-left spatial attention. METHODS: The subjects were veterans with amputation of one upper or lower limb. All subjects performed horizontal line bisections in their left, middle and right body-centered space. RESULTS: Following right upper limb amputation, there appears to be a reduction of the normal left-sided bias (pseudoneglect) primarily for lines presented in the right body hemispace. CONCLUSIONS: This amputation-induced alteration of attentional bias might be related to changes in the body schema, a compensatory strategy, or alterations of scanning patterns. Further studies are needed to reproduce these results and to learn the underlying brain mechanism.