The effect of paragigantocellularis lateralis lesion on conditioned place preference (CPP) in presence or absence of a 2 adrenergic agonist (clonidine) in male rats

Abstract

The nucleus paragigantocellularis lateralis (LPGi) is located in the rostral ventrolateral medulla (RVLM), a brain stem region that regulates homeostatic functions such as blood pressure and cardiovascular reflexes, respiration, pain and opiate withdrawal syndrome. LPGi has many anatomical relationships with important nuclei such as arcute nucleus, caudal raphe nucleus, periaqueductal gray (PAG), locus coeruleus (LC), and dentate. In this study we have examined the role of LPGi in the conditioned place preference (CPP) induced by morphine in the presence and absence of clonidine in the rat. We used 49 male N-MRI rats which were divided into 7 groups randomly: 1: Control, 2: Control+saline, 3: sham control, 4: lesion, 5: lesion +0.02 mg/kg clonidine, 6: lesion +0.2 mg/kg clonidine, 7: lesion +2 mg/kg clonidine. Animals were anaesthetized with ketamine (110 mg/kg) and rampune (Xylazine) (3 mg/kg) mixture. In the process of surgery LPGi nucleus has been destroyed bilaterally by DC electrical current (1 mA, 6 second), with stainless steel electrode placed in stereotaxic coordinates of (AP = 11.8, Lat +/- 1.86 and Depth = 10.5). After the recovery period, they were treated with clonidine one hour before the application of Hand's method to induce CPP. We have not found any significant differences between the results of control, control+saline and sham groups in the CPP test but there is a significant increase in the CPP time between sham and LPGi lesion+saline groups (P < 0.019). Clonidine at different doses (0.02, 0.2 and 2 mg/kg) have decreased CPP time in LPGi lesioned group in comparison with lesioned+saline group as well (p < 0.002). In this study we have also demonstrated that clonidine has not any effects on the CPP time in the intact animals. Our results indicate that LPGi lesion induces CPP. It seems that LPGi is involved in drug reinforcements and also LPGi lesion induces sensitivity to alpha2 adrenergic agonist.