Clonidine maintains intrathecal self-administration in rats following spinal nerve ligation

Abstract

Clonidine is approved for spinal administration against neuropathic pain, and reverses both spontaneous and elicited pain in humans following spinal administration. Rodent studies that seek to model pharmacology in pain states have historically relied on reflexive withdrawal from noxious stimuli as the primary endpoint. Drug self-administration studies have face validity in the drug abuse field for modeling drug abuse in humans, however, this methodology has not been applied to address issues related to drug seeking behaviors that may be relevant for other human populations, such as patients with neuropathic pain. Rats without spinal nerve ligation (SNL) failed to acquire intrathecal clonidine self-administration over 10 days of access. Rats were found to self-administer intrathecal infusions of clonidine following SNL in a stable and dose-responsive manner, however, and clonidine was self-administered throughout the day with 66% of total drug intake occurring during the dark cycle. Substitution of clonidine with saline or with clonidine and the α2-adrenoceptor antagonist idazoxan resulted in extinction of responding in SNL animals. Food reinforcement was initially decreased in SNL rats self-administering clonidine compared to normal animals, however, tolerance developed to this effect of clonidine in SNL rats after 5 days. These data demonstrate that drug self-administration can be applied to questions other than drug abuse, and provides an additional measure for development of novel therapeutic strategies for chronic pain treatment.