ABSTRACT
INTRODUCTION: Inflammatory pain is a common sign of chronic diseases. Some brain regions such as locus coeruleus (LC) of the brainstem nor-epinephrine (NE) system have a key role in The mechanisms of the pain modulation and dependence. Bupropion synthesized as an antidepressant, but it is using for smoke cessation. It can change morphine withdrawal signs such as pain related behaviors. This study tested the acute effect of intra-LC microinfusion of bupropion on the formalin-induced pain behavior in rats. METHODS: Wistar male rats were divided into 6 groups (control-naïve, control-operated, shamoperated, and 3 treated groups with 10(-2), 10(-3), 10(-4) mol/µl intra-LC of bupropion). The injection guide cannulae were implanted into LC nuclei bilaterally by stereotaxic coordinated surgery under sterile condition. The sham group received normal saline as drug vehicle but control groups had no intra-LC injections. Formalin (50 µl, 2.5%) was injected subcutaneously in plantar region of the right hindpaw in all animals (30 min after drug administration in treated animals). Nociceptive signs were observed continuously and registered on-line each minute. Common pain scoring was used for pain assessment. RESULTS: The analysis of data by one-way ANOVA showed that bupropion can reduce pain behavior scores significantly. Bupropion reduced total pain score in the phase 01 (60%) and phase 02 (52%) of maximal behavior compared to the sham group, dose dependently and significantly. The pain scores of controls and sham groups had no significant difference. DISCUSSION: The results showed that bupropion has analgesic effects on LC neurons and can alter the neurochemical involvement of LC in pain process. Bupropion has different and significant effect on early and late phases of formalin test.
ABSTRACT
INTRODUCTION: The most common interpretation for the mechanisms of antidepression is the increase of the brain monoamine levels such as dopamine (DA). The increase of DA can reduce depression but it can also decrease the monoamine release because of autoreceptor inhibition. Although bupropion can decrease the dopamine release, there is evidence about stimulatory effects of chronic application of bupropion on ventral tegmental area (VTA) neurons. In this study, the intra-VTA acute microinfusion of bupropion on putative VTA non-Dopaminergic (VTA-nonDA) neuronal firing rates was evaluated by a single neuron recording technique. METHODS: Animals were divided into 7 groups (sham, and 6 bupropion-microinfused groups with 1, 10(-1), 10(-2), 10(-3), 10(-4), and 10(-5) mol, 1 µl/3 min, intra-VTA). A single neuron recording technique was done according to the stereotaxic coordination. After 10 min baseline recording, ACSF or bupropion was microinfused. The recording continued to recovery period in the treated groups. The prestimulus time (PST) and interspike interval (ISI) histograms were calculated for every single unit. The assessment of the drug effect was carried out by one-way analysis of variance (ANOVA) and Post-hoc test. RESULTS: 126 non-DA neurons were separated. Bupropion could inhibit 116 neurons and 11 neurons had no significant response. Maximum inhibition was 79.1% of baseline firing rate with 44.3 min duration. The inhibitory effect of bupropion was dose-dependent. DISCUSSION: The acute inhibitory effects of bupropion on VTA-nonDA neurons can explain the fast inhibitory effects of bupropion and other antidepressants on the VTA. These data can explain some side effects of antidepressants.
