[ effects of intra-locus coeruleus injection of dopamine D2 receptor agents on Naloxone withdrawal signs in Morphine-dependent rats]

ABSTRACT

Opiate-induced addiction is a main social problem in Iran. As treatment of this problem is a health priority among the medical community, studies on this topic are very crucial. The exact mechanism of dependence on opiates and their withdrawal syndrome remain unclear. It seems that dopaminergic system and locus coeruleus [LC] have an important role in the expression of somatic signs during opioids withdrawal. The LC has been shown to contain significant levels of dopamine [DA]. In the present study, the effects of different D2 dopaminergic receptor agonist and antagonist administration in the LC on withdrawal sign expression in morphine dependence is investigated in rats. Adult male Wistar rats, weighing 220-280 g were divided into eight groups [n=8]. Two cannulae were stereotaxically implanted bilaterally into the LC of each rat. After a one-week recovery, seven groups were rendered dependent on morphine by subcutaneous injection during a seven-day period. Non-dependent control animals received saline according to the same protocol. Animals received bilateral intra-LC injections of saline [1 micro g/site] and quinpirole [0.1, 0.3 and 0.5 micro g/site, a D2 agonist] 15 min and sulpiride [5, 15 and 30 micro g/site, a D2 antagonist] 30 min prior to naloxone injection about 24 hours after the last dose of morphine or saline according to their respective group. To calculate the total withdrawal score, as an index of withdrawal syndrome, 20 different withdrawal signs were assessed and the scores of the intensity of these withdrawal signs were added. Total withdrawal scores were significantly decreased by quinpirole [0.1micro g/site] and sulpiride [15 and 30 micro g/site]. The D2 dopaminergic system in the LC may be involved in the morphine-induced dependency in rats. Further studies are needed to define the mechanism of this dependency in order to improve methods for the rehabilitation of addicts