In this study, effects of intrahippocampal (IH) injection of adrenoceptor agents on imipramine-induced impairment of memory retention were investigated. Imipramine (2-8 µg/rat) decreased retention latencies in passive avoidance task.Administration of α1. -adrenoceptor agonist, phenylephrine (0.05 µg/rat) and prazosin, an α1- adrenoceptor antagonist (0.5 µg/rat) did not alter the response of imipramine. Low doses of phenylephrine (0.005 and 0.015 µg/rat) decreased, while higher doses of the drug (0.025 and 0.05 µg/rat) increased memory retention. The effect of phenylephrine was not altered by (0.5 and 1 µg/rat) prazosin pretreatment however, prazosin alone decreased retention latencies. The α2-adrenocetor antagonist, yohimbine (0.5 and 1 µg/rat) decreased the response induced by imipramine. However, the α2 adrenoceptor agonist, clonidine (0.08 µg/rat) did not alter the response of the drug. Clonidine (0.15 and 0.3 µg/rat), by itself, decreased but yohimbine (1 and 2 µg/rat) increased retention latencies. Yohimbine pretreatment decreased the response of clonidine.It is concluded that adrenoceptor mechanism(s) may be involved in imipramine-induced impairment of memory retention.

In this study, the effect of α-adrenoceptor agents on imipramine-induced antinociception was investigated using formalin test. Intraperitoneal (IP) administration of imipramine at different doses (10-80 mg/kg) induced antinociception in both phases of formalin test. In addition, intracerebroventricular (ICV) injection of imipramine (1, 5, and 10 µg/rat) did not elicit any effect, although ICV injection of clonidine, an aradrenoceptor agonist at doses of 0.05-0.8 µg/rat also elicited antinociception in both phases of the test. Furthermore, clonidine increases the antinociception induced by imipramine and yohimbine, an α2-aradrenoceptor antagonist at a dose of 2 µg/rat (ICV) reduced the response to imipramine at a low dose (10 mg/kg, IP) and clonidine (0.05 µg/rat, ICV), but did not alter the response induced by higher doses of imipramine (20 and 40 mg/kg) alone or in combination with clonidine. Yohimbine by itself elicited no response. Meanwhile, phenylephrine (0.07-1.5 µg/rat, ICV), a α1-adrenoceptor agonist induced antinociception in both phases of formalin test, but did not alter the imipramine-induced antinociception. The α1-adrenoceptor antagonist, prazocin neither elicited antinociception nor altered the imipramine response. Yohimbine (2 µg/rat, ICV) in combination with prazocin (0.5 µg/rat, ICV) further inhibited the response for imipramine alone or in combination with clonidine. Taken together, it is concluded that aradrenoceptor-mediated mechanism might be involved in the development of imipramine-induced antinociception.

Background: This experiment was planned to investigate the nature of α- and β- adrenoceptor in blood vessels supplying the posterior capsule of the acutely inflamed rabbit knee joint, and results were compared to findings from previous experiments on the normal joint, to assess any alteration which may occur in the adrenoceptor profile due to the inflammation process.  Material and Methods: This study was conducted with 30 white new zealanian rabbits under pentobarbital induced general anes thesia they were divided into two α and β-groups. Blood flow of posterior articular nerve of knee was measured by laser flow meter. α and β-gonist drugs were injected intra-arterial in the presence and absence of their antagonists. Acute inflammation was induced by intra-articular karaginine. Posterior articular nerve was stimulated by nerve stimulator.  Results: Electrical stimulation of the posterior articular nerve resulted in vasoconstriction which was reversed to vasodilatation by phentolamine and yohimbine. The dose – response curves intra-arterial injection of α- adrenoceptor agonists showed a rank-order potency of: adrenaline= phenylephrine= clonidine. The adrenaline dose-response curve was shifted to the right by administration of antagonists with a rank-order potency of: phentolamin= yohimbine= prazosin. At this stage of the experiment there was an equal response of α1-and α2- adrenoceptors in blood vessels of the acutely inflamed rabbit knee joint. In other two groups of animals the neutrally mediated vasodilatation, which appeared after administration of phentolamine, was completely blocked by propranolol, and was reduced to about 50% by atenolol. The dose-response curves in intra –arterial injection of β- adrenoceptor agonists showed a rank-order potency of: isoprenaline> salbutamol = dobutamine. The isoprenaline dose- response curve was shifted to the right by administration of antagonists with a rank-order potency of: propranolol> atenolol. This experiment also showed an almost equal response of β1-and β 2- adrenoceptors in blood vessels of the acutely inflamed rabbit knee joint. Overall, compared to previous experiments on the normal joint in which α1-and β1- adrenoceptor responses predominated, acute inflammation resulted in a shift from α2-towards α1- and from β1-towards β 2- adrenoceptors responses.Conclusion: Generally in comparison to previouse experimentas on the normal joint in which α1 and β1 receptor responses predominated, acute inflammation resulted in a shift from α2 towards α1 and β1 towards β2 – receptor responses.

BACKGROUND AND OBJECTIVE: The joint vascular-α adrenoceptors change due to acute inflammation from a majority of α-2 to an equality of α -1 and α -2 receptors. This study was done to investigate the role of sympathetic nerves in nerve induced vasoconstriction and changes in joint vascular adrenoceptors due to chronic inflammation.METHODS: In 21 NZW rabbits, knee joint chronic inflammation was induced by Antigen Induced Arthritis (AIA) method. In experiment day, animals were anesthetized and the carotid artery was cannulated to record blood pressure and jugular vein for injection the anesthetic drugs. The medial belly of gastrocnemius muscle was removed to get access to posterior knee joint capsule and the blood flow was measured by laser flowmetry. FINDINGS: Electrical stimulation of PAN resulted in 25.6± 5.6 percent reduction of blood flow measured by laser Doppler flowmetry technique. The half of this response was blocked by prazosine (α1-agonists) and the other half by youhimbin (α 2- agonists) to11.8± 4.1 and 10.9±12.4 percent reduction, respectively but phentolamine completely blocked the constrictor response and reversed it to vasodilation (2.5± 2.1%). Close intra-arterial injection of different doses of α-agonists reduced the joint blood flow by the potency rank order of adrenaline> clonidine= phenylepherine, suggesting a balance between α 1 and α2 adrenoceptors. In previous studies, in normal and acutely inflamed knee joint, stimulation of PAN resulted in 36.5±4 and 9.9±2.25 percent reduction of blood flow, respectively that indicated acute inflammation reduces the role of sympathetic nerves in the regulation of knee joint blood flow.CONCLUSION: Overall this study showed a balance between α-adrenoceptor subtypes in the chronically inflamed knee joint blood vessels and compared to results of our pervious investigation on acutely inflamed of rabbit knee joint. The sympathetic vasoconstrictor response was mostly recovered without more alteration in α- adrenoceptor subtypes that happened in acute inflammation.

Objective: This study aimed to evaluate the effect of parazosin (alpha-l adrenergic receptor antagonist), yohimbine (alpha-2 adrenergic receptor antagonist), bicuculline (GABAA receptor antagonist), CGP35348 (GABAB receptor antagonist), and lidocaine (calcium channel blocker) on the analgesic effect of carbamazepine on white NMRI-mice, in the both phases of the formalin test. Method: In this interventional experiment, the analgesic effects of carbamzepine, prazosin, yohimbine, bicuculline, CGP35348, and lidocaine were tested by performing an intraperitoneal injections during the formalin test. Also the effect of the mentioned drugs on the analgesic effect of carbamazepine was assessed. The formalin test was used as a model of chronic pain, in which formalin 0.5% was infused into the plantar surface of the mouse foot as the painful stimulus animal's response was observed. Data at minutes 0-5 were considered as measures of acute pain, data at minutes 5-16 were considered as the chronic pain. Results: Different doses of intraperitoneal injections of carbamazepine (3, 5,7, 15,30 mg/kg), lidocaine (5, 10,20 mg/kg), prazosin (0.125, 0.25, 0.5 mg/kg), yohembine (0.25, 0.5 mg/kg), bicuculline (1, 3, 5 mg/kg), and CGP35348 (100, 200 mg/kg) showed analgesic effects in the both phases of the formalin test. The analgesic effect of carbamazepine was not influenced by injection of other medications except lidocaine. Simultaneous administration of lidocaine augmented the analgesic effect of carbamazepine in the first phase of the formalin test but not the second. It should be mentioned that the administration of bicuculline (0.75 mg/kg) was associated with induction of hyperalgesia in the second phase, probably by blocking a group of GABA receptors and thus inducing pain. Conclusion: With regard to the effect of lidocaine on carbamazepine in the acute phase it is suggested that at least a part of the analgesic effect of the carbamazepine is related to a sodium channel mechanisms.

Background: Amitryptiline and other tricyclic antidepressants are widely used in chronic pain states in humans. The clear expression of local analgesic action with antidepressants raises the possibility that this class of agents could be given topically and may be useful as peripherally acting analgesics in humans. Methods and Materials: In this study, effect of alpha-2 adrenoceptors and 5-HT2 serotonergic receptors antagonist on the analgesia induced by amitryptiline in rat was investigated. Subcutaneous injection of different doses of amitryptiline (4,8,16 mg/kg) induces dose-related analgesia in rat. Results: The alpha-2 adrenoceptors antagonist, yohimbine (2mg/kg) reduced the response induced by amitryptiline but 5-HT2 serotonergic receptors antagonist, ketanserin (lmg/kg) increased the response induced by amitryptiline. Conclusions: It seems that Ketanserin increased the pain threshold. It may be concluded that amitryptiline-induced analgesia is through alpha2- adrenoceptors mechanism.

Introduction: Oxytocin is a active neuropeptide of central nervous system. In this study the effects of naloxone (opioid receptor antagonist) and yohimbine (a-2 adrenergic receptor antagonist) on analgesic effect of oxytocin applied into the locus coeruleus (LC) nucleus were investigated.Methods: Adult male Wistar rats were used. Animals divided into different groups receiving saline, oxytocin (3 nmol / 2ml), naloxone (3 nmol / 2ml) + oxytocin, yohimbine (3 nmol / 2ml) + oxytocin, and naloxone + yohimbine + oxytocin. Hot-plate and tail-flick tests were used to evaluate pain threshold.Results: Data showed that the injection of oxytocin into the LC nucleus increases the response time to thermal stimulations in both tail flick and hot plate tests. Injection of naloxone and yohimbine either separately and or in combination inhibite the antinociception effect of oxytocin.Conclusion: It seems that oxytocin induces its inhibitory effect on acute pain via LC nucleus. This effect is probably mediated by the combination of opioid and a-2 adrenergic systems.

Introduction: Locus coeruleus (LC) nucleus modulates certain physiological behaviors such as pain, anxiety, awake, sleep, memory and learning. Some studies have shown that the LC nucleus has both adrenergic neurons and a2-adrenoceptors, and also receives oxytocinergic projections from the paraventricular nucleus of the hypothalamus. The effect and mechanism of this neuropeptide is not fully understood. Considering that the chronic usage of oxytocin decreases anxiety, in the present study the effect of acute administration of oxytocin in the locus coeruleus and its interaction with a2 adrenoceptors on anxiety induced vogel’s test in male adult rats were investigated. Materials and Methods: Male adult wistar rats weighing 285±15 grams were divided into 6 groups: 1) Receiving saline, 2) oxytocin (2ng/2ml), 3) yohimbine (3.3mg/2ml), 4) receiving saline + yohimbine, 5) saline+ oxytocin and 6) yohimbine+oxytocin in locus coeruleus nucleus. Number of received shocks during water drinking was evaluated as an anxiety behavior for 15 minutes in Vogel's test. Results: Oxytocin reduced number of shocks received (Anxiogenic effect). Blocking of a2 adrenoceptors by yohimbine decreased number of shocks received. Anxiogenic effect of oxytocin increased in presence of yohimbine. Conclusion: It seems that the LC a2-adrenoceptors modulate anxiety and the anxiogenic effect of oxytocin and this effect can be eliminated by the blocking of the a2-adrenoceptors.