Objectives: The term of aggression with different meaning applied to wide range of integrative behaviors. Two main classes of aggressive behavior include defensive and offensive. The defensive behavior is tactics for protection of vulnerable parts of body but offensive behaviors is defense against intruders. In the natural state defensive animals can flee from the territory but in restrained condition such as laboratory animals, they show flight, crouching, up right defensive posture. The VTA (VENTRAL TEGMENTAL AREA) with dominant dopaminergic neurons is widely implicated in psychotic disorders. Bupropion as an antidepressant agent is used for smoke cessation widely under FDA approval. The clinical data have showed that it can induce aggressive behavior as side effect. Despite clinical evidence, the mechanism of Bupropion on aggression is not known well.Methods: Rats defensive aggression were registered online and offline in control, sham and 3 doses of bupropion. Intra VTA injection was carried out by standard stereotaxic surgery.Results: Aggressive behaviors were only affected by 0.25 mg of bupropion and there were no significant difference between other groups.Conclusion: These data showed that bupropion have complex effect on aggression behavior. Bupropion can inhibit reuptake of dopamine and have effect on VTA neuronal activity for modulation of aggression.

Introduction: Antidepressants can modulate brain monoamines by acting on pre-synaptic and postsynaptic receptors. Autoreceptors can reduce the monoamines effect on the somatodendritic or pre-synaptic regions despite its postsynaptic counter effects. The direct effect of some antidepressants is related to its temporal and spatial bioavailability in the vicinity of these receptors (still a matter of controversies). This research evaluated the direct effect of acute bupropion on the VENTRAL TEGMENTAL AREA (VTA) dopaminergic neuronal firing rate. Methods: Male Wistar rats were divided into intracerebroventricular and microiontophoretic groups with 14 subgroups (n=5 in each subgroup). Amounts of 1, 0. 5, 0. 1, 0. 01, 0. 001, and 0. 0001 mol of bupropion (5 μ L/3 min) were microinfused to the first group and then the ejected amounts of bupropion at-500,-300,-150,-50 nA of electrical currents (1 mol, pH=4. 5, 5 min) were applied to the second group. The control and sham subgroups were studied in each group, too. The units with stable firing rates were extracted, and the effect of bupropion was evaluated statistically with a P value less than 0. 05 as the level of significance. Results: The highest amount of bupropion in the intracerebroventricular application could excite 42% of the neurons and inhibit 56% of them, but the highest amount of microiontophoretic application of bupropion could inhibit 97. 5% of the neurons. The neuronal response to bupropion was dose-dependent in all treated groups. Conclusion: The dual effects of intracerebroventricular bupropion on the VTA dopaminergic neurons but solo inhibitory effect of its microiontophoretic application reflect the intra-VTA and extra-VTA heterogenic cellular and molecular control over the dopaminergic outflow that can be mediated by different receptors. The dopamine autoreceptors on the VTA dopaminergic neurons have complex modulatory effects on the dopaminergic response.

Background &Aims: Dopaminergic neurons in the VENTRAL TEGMENTAL AREA (VTA) are involved in dependence, tolerance, and withdrawal syndrome to opiates. The aim of this study was to investigate the effect of temporary inactivation of VTA on heroin dependency and withdrawal syndrome sign (WSS).Materials & Methods: Male Wistar rats (250-300g) were anaesthetized and implanted with catheters into the right jugular vein. A stainless steel canulae was bilaterally implanted to VTA in related groups. After recovery, the animals were fitted and the external end of the catheter was connected with a pump, then were placed in the self-administration (SA) apparatus daily, for 10 days. Active lever switched on the infusion pump injecting 0.1ml of heroin hydrochloride solution (1 mg/ml) or saline. The experimental groups were as follows (n=6): saline, intact and inhibited VTA (which received 20ml of lidocaine 2% before SA daily). In the end of the 10th day, naloxone 2mg/kg. IP was injected and animals were studied for heroin WSS.Results: Comparison of active and passive lever pressing inside each group and active lever between all groups showed a significant difference (p<0.05 and p<0.001 respectively). After naloxone injection, the animals in the group intact VTA merely showed WSS (P<0.001).Discussion: Temporary inactivation of VTA can prevent the reinforcing effect of heroin and the development of dependence on it. Probably with further studies, handling of VTA can be a useful management for heroin addiction.

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 ml/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.

Background and aim: VENTRAL TEGMENTAL AREA (VTA) is located in the mesencephalon and it is one of the main nuclei that play a major role in drug abuse or addiction. In this study we investigated the effect of electrical stimulation of the VTA on addiction to morphine.Methods: Intravenous self-administration was used to quantify the level of drug-dependence. Twenty-four Wistar rats were divided into three groups: 1) Sham or saline group that had surgery and received saline by self-administration. 2) Control or morphine group that had surgery and received morphine by self-administration. 3) Case or morphine + .stimulation (25 µA.;100 Hz; 0.14 ms period; for 10 minutes) group that had surgery and received electrical stimulation 15 minutes before morphine self-administration.Results: Addiction was seen only in the morphine group, and electrical stimulation of the VTA prevented the addiction.Conclusion: Electrical current stimulates all type of the neurons in the VTA. Since dopaminergic neurons comprise two-third of its neurons, VTA stimulation may cause the release of dopamine in the nucleus accumbence and produce rewards so that the animal needs no further rewards from morphine.

Background: Anxiety is a complex phenomenon with important results. In fact anxiety is a biologic process that has repetitive biological and physiological effect on the biological structure of brine. From long time ago anxiety and fear has bean one of the important psychological issues and for the control of anxiety different drugs with different mechanisms have been presented and understanding mechanisms that are involved lead us to newer drugs discovery. In this research the effect of morphine on the anxiety in the adult Male rats in the VENTRAL TEGMENTAL AREA (VTA) and Nucleus Accumbens (NAc) was studied.Methods: The elevated plus maze was used in combination with the percentage of time spent in the open arms of the maze (OAT%) and the percentage of entries into the open arms (OAE%) to measure anxiety. Increases in the OAT% and OAE% indicate an anxiolytic effect (reduction in anxiety), whereas decreases in the OAE% and OAT% indicate an anxiogenic effect. Adult male rats, weighing 200-240 grams, underwent surgery. After five days, the rats were injected with saline and three different doses of morphine (2.5, 5, and 7.5 ml/rat). Experiment one included the injections into the VTA. In the second experiment, these injections were in the NAc. Behavioral tests were conducted between 12 pm and 4 pm and each animal was used once for each experiment.Results: In the first experiment, although these doses of morphine injected into the TVA had no effect on the OAE%, a dose of 5ml/rat increased the OAT%, showing a decrease in the animals’ anxiety. In the second experiment, doses of 2.5ml/rat injected into the NAc induced a significant increase in the OAT% and OAE%, there by displaying decreased anxiety in the animal. However, no significant change in the activity of the animals was observed.Conclusion: As a Result of these experiments, it seems that different doses of morphine can decrease anxiety, probably through interaction with gabaergic system.