Tehran University Medical Journal

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Background: 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.
Methods: 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 μg/site) and quinpirole (0.1, 0.3 and 0.5 μg/site, a D2 agonist) 15 min and sulpiride (5, 15 and 30 μg/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.
Results: Total withdrawal scores were significantly decreased by quinpirole (0.1µg/site) and sulpiride (15 and 30 µg/site).
Conclusion: 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.

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Background: Dopaminergic is the most important neurotransmitter is fear. The dopaminergic mesolimbic pathway has essential role in excitable behavior, and it's role in Parkinson disease. The aim of this research in study, the effect of dopaminergic pathway in fear response.
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 fear. Increases in the OAT% and OAE% indicate an anxiolytic effect (reduction in anxiety), whereas decreases in the OAE% and OAT% indicate an anxiogenic effect. After five days, the rats were injected with saline and different doses of sulpiride and Bromocriptine.
Results: Results showed that intracerebroventricular administration of sulpiride, in the doses of 5, 20μg/rat and bromocriptine, D2 agonist in doses 65, 95μg/rat produced a significant effect comparing to sham groups (p<0.05). While intracerebroventricular administration of sulpiride 15, 10μg/rat, and bromocriptine 70, 80μg/rat, did not show any significant effect comparing with sham group (p<0.05). In the current research intracerebroventricular administration of sulpiride, D2 antagonist at the doses of 5, 10, 15, 20μg/rat and Bromocriptine, D2 agonist in the doses of 65, 70, 80, 95μg/rat were used and theire effect on the fear behavior were studied.
Conclusions: The possible effect of Dopaminergic system in the fear process, especially D2 receptor increase fear.

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Background: Use of certain antipsychotic drugs has severe effects on fertility in males. Hypothalamus and hypophysial impressions and changes in plasma hormones concentration like prolactin, LH and FSH can affect sperm production. In this study, we investigated the effects of sulpiride on sperm quality, maturation and DNA damage.

Methods: Twenty for adult male mice (age: 6-8 weeks) were divided into three groups. The treatment group received 40 mg/kg sulpiride solution and the control sham group was given carrier of the drug intraperitoneally (IP) daily for 45 days but the control group received nothing. Finally, all the mice were sacrificed by cervical dislocation and their cauda epididymis were removed surgically. The excised specimens were placed in 1 ml HTF medium and incubated for 30 min in CO2 incubator to allow the spermatozoa to swim out. Later, sperm count, motility and viability were analyzed. Additionally, sperm chromatin quality and DNA integrity were assessed by aniline blue and acridine orange staining.

Results: Significant decrease in sperm motility and count were observed in the treatment group while the number of abnormal sperm increased as compared with the other two groups. Sperm viability and DNA maturation showed significant reduction and the rate of DNA damage increased in comparison with the control sham and the control groups (P<0.05).

Conclusion: The study showed that sulpiride has negative effects on sperm parameters in treated animals and in some cases it could cause secondary infertility.