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Anesthesiology. 2012 May;116(5):1116-23. doi: 10.1097/ALN.0b013e3182518be3.

Intracranial self-stimulation of the paraventricular nucleus of the hypothalamus: increased faciliation by morphine compared to cocaine.

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Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.



Neuropathic pain attenuates opioid facilitation of rewarding electrical stimulation of limbic dopaminergic pathways originating from the ventral tegmental area. Whether neuropathic pain alters opioid effects of other brain-reward systems is unknown.


Control and spinal nerve-ligated (SNL) rats had electrodes implanted into the paraventricular nucleus (PVN) of the hypothalamus or medial forebrain bundle. Control and SNL rats were trained to lever-press for intracranial self-stimulation (ICSS), and modulation by morphine or cocaine was assessed.


Control and SNL rats lever-pressed for stimulation of the PVN and medial forebrain bundle. Morphine produced greater reductions in the frequency at which rats emitted 50% of maximal responding for PVN ICSS (maximal effect 24.67 ± 4.60 [mean ± SEM] and 24.11 ± 5.96 in SNL [n = 6] and control [n = 8] rats, respectively, compared with medial forebrain bundle ICSS (12.38 ± 6.77 [n = 8] and 12.69 ± 1.55 [n = 7]). In contrast, cocaine was less efficacious in potentiating PVN ICSS (maximal effect 11.76 ± 2.86 and 12.38 ± 4.01 in SNL [n = 12] and control [n = 8] rats, respectively) compared with medial forebrain bundle ICSS (30.58 ± 3.40 [n = 9] and 27.55 ± 4.51 [n = 7]).


PVN ICSS is facilitated to a greater extent by morphine than cocaine, and the effects of each drug on this behavior are unaltered after spinal nerve ligation. These effects contrast those observed with direct stimulation of limbic dopamine pathways, suggesting that the PVN may have a greater role in the reinforcing effects of opioids than classic limbic regions, particularly in the presence of chronic pain.

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