The Effect of Reversible Locus Coeruleus (LC) on I.V Self-Administration of Morphine and Morphine Withdrawal Syndrome(MWS) Signs in Rats

Locus coeruleus (LC) has been hypothesized to play an important role in a variety of behaviors and opiate withdrawal. This study was designed to determine the effects of reversible inactivation of LC on self-administration of morphine and morphine- withdrawal syndrome signs (MWS). 24 male rats (250-300gr) were surgically implanted bilaterally with cannula in LC then implanted with catheters in the right jugular vein. The rats were tested in 2 groups:Control(saline) and morphine. Morphine group was divided into 3 subgroups: control, sham-operated and LC-inactivated group where they received 1µL 2% Lidocaine 5 minutes prior to testing. Animals were allowed to self-administer morphine (1mg/infusion) during 10 consecutive days for 2 hours. The number of lever pressing was recorded. At the end of the training day all groups received naloxone (2mg/kg I.P) and MWS were studied for 30 minutes. LC inactivation prevents the development of tolerance and dependence on morphine and greatly attenuates morphine-withdrawal syndrome. LC inactivation not only attenuates morphine withdrawal syndrome but also prevents morphine tolerance and dependence in rats.