The activity of D2 dopamine receptors of the ventral tegmental area changed the induced- cognitive responses of the lateral hypothalamic cholinergic stimulation following neuropathic pain.

BACKGROUND: Dopaminergic neurons within the ventral tegmental area (VTA) is involved in the development of cognitive dysfunction during chronic pain. It is controlling cognitive behaviors via its various projection pathways to different areas in the brain including lateral hypothalamus (LH). The activation of LH induced analgesia during chronic pain. In the current study, we assessed whether D2 dopamine receptors activity within the VTA can change the induced-cognitive responses of LH following its cholinergic stimulation during neuropathic pain in rats. Aditionally, we assessed whether cholinergic stimulation of LH can change firing rate of VTA neurons.

METHODS: Male Wistar rats were implanted with two separate cannulae into the LH and VTA on the same side. After 4 days' recovery of cannulation surgery, animals underwent second surgery for induction of neuropathic pain (chronic constriction injury of sciatic nerve, CCI). Citicoline (1 µg/1µl normal saline), as an acetylcholine precursor, that activates the LH projecting neurons, were microinjected into the LH. In the other groups, D2-like dopamine receptor antagonist, sulpiride (1 µg/1µl normal saline) or agonist, bromocriptine (1 µg/1µl normal saline) were microinjected into VTA, 5 min prior intra-LH injection of citicoline. Cognitive and electrophysiology studies were assessed 15-30 minutes after drug injection.

RESULTS: Stimulation of LH via citicoline significantly induced analgesic and learning/memory enhancer effects. Additionally, intra-VTA injection of bromocriptine significantly increased analgesic and learning/memory enhancer effects of LH. Interestingly, sulpiride significantly decreased analgesic and learning/memory enhancer effects of LH. Stimulation of LH via citicoline effectively increased firing rate of VTA neurons. Intra-VTA injection of bromocriptine and sulpiride significantly increased and decreased firing rate of VTA neurons, respectively.

CONCLUSION: The present study suggest that the analgesic and memory enhancer effects which produced by LH cholinergic stimulation is mediated by D2-like dopamine receptors of VTA in neuropathic pain. Additionally, the cholinergic stimulation of LH via citicoline can increase firing rate of VTA neurons during neuropathic pain and intra-VTA injection of sulpiride effectively reversed the effects of citicoline on firing rate of VTA neurons.