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The neurotransmitter dopamine (DA) regulates various physiological and psychological functions, such as movement, motivation, behavior, and learning. DA exerts its function through DA receptors and a series of studies have reported the role of DAergic receptors in preventing DAergic neuronal degeneration. Here, we studied the DA receptor-mediated neuroprotective effect of the D2-like receptor agonists against 6-hydroxydopamine (6-OHDA)-induced DAergic neurodegeneration. D2-like receptor agonists were administered in the substantia nigra in vivo and to primary cultured neurons. Treatment of 6-OHDA decreased tyrosine hydroxylase (TH) and paraplegin (mitochondrial regulation protein) immunoreactivity, whereas pretreatment with quinpirole (a full D2-like receptor agonist) preserved TH and paraplegin reactivity. This led us to test which DA receptors were necessary for the neuroprotective effect and whether paraplegin can be regulated by D2 or D3 receptor agonists. Pretreatment with the D2 receptor selective agonist, sumanirole, did not preserve TH and paraplegin reactivity from 6-OHDA. However, the D3 receptor agonist, pramipexole, protected TH reactivity and restored paraplegin expression to the control level in the presence of 6-OHDA. Interestingly, pretreatment with the D3 receptor antagonist GR103691 reduced TH and paraplegin expression levels. These results suggest that the D3 receptor agonist may protect DA neurons from the effect of 6-OHDA through the modulation of the mitochondrial regulation protein paraplegin.

The effects of topical application of interleukin-6 (IL-6) on the short and long latency evoked unit responses of the neurones in the primary somatosensory (SI) cortex were determined quantitatively in anaesthetized rats. IL-6 (0.01, 0.1, 1.0 units) significantly suppressed (-15.13 +/- 3.4%) short latency afferent sensory responses, while it induced profound facilitation (+464.74 +/- 132.7%) of long latency responses in a dose-dependent manner. IL-6-induced afferent modulations fully recovered by 60 min after drug administration. In control experiments, saline solution containing 0.2% bovine serum albumin, used as a vehicle, did not affect afferent sensory transmission. Implications of these results are discussed with reference to the different somatosensory functions of short and long latency response components in the SI cortex.

Activity-dependent changes of the conduction latency of single A beta fibers of primary afferent neurons were characterized in both neuropathic (L4 and L6 ligated) and normal rats. Activity-dependent increases in conduction latency of dorsal root fibers in neuropathic rats were significantly stronger than those in normal rats. Different profiles of activity dependence were also observed between injured and adjacent intact dorsal root fibers of neuropathic rats. However, activity-dependent latency changes in sciatic nerves distal to the dorsal root ganglion were not different between neuropathic and normal rats. These results suggest that partial nerve injury induces activity-dependent excitability changes in the dorsal root fibers of neuropathic rat and that these changes may be responsible for the altered sensory processing such as those seen in allodynia.

Activity-dependent changes of conduction velocity (CV) and conduction block in single A(delta) fibers of primary afferent neurons were characterized in a rat model of neuropathy (NP). Injured dorsal root (DR) fiber in NP rats exhibited profoundly greater decreases of CV following impulse activity than did DR fiber in normal rats. Activity-dependent conduction block was absent up to 100 Hz of activity rate in DR fiber of NP rats, but was present above 25 Hz in normal rats. Profiles of activity dependence in sciatic fibers were similar in both NP and normal rats. These results suggest that nerve injury may alter activity-dependent hypoexcitability of A(delta) DR fibers. Furthermore, this excitability change may be responsible for the elevated pain perception in neuropathy.

The effect of topical application of interleukin 2 (IL-2) on afferent sensory transmission to the neurones in the primary somatosensory (SI) cortex was determined quantitatively in anaesthetized rats. IL-2 (0.1, 1.0, 5.0 units) significantly suppressed afferent sensory transmission in SI cortical neurones (n = 19) in a dose-dependent manner. IL-2-induced suppression fully recovered by 60 min after drug. In control experiments, saline solution containing 0.2% bovine serum albumin, used as a vehicle, did not affect afferent sensory transmission. Our results suggest that IL-2 and its receptor present in the SI cortex may be involved in the processing of afferent sensory information.