Suicidal attempt and psychiatric disorders in Iran

This study is part of broader research aimed to determine the lifetime prevalence and pattern of comorbidity on self-reported suicidal attempts in the general population of Iran. Overall, 25,180 subjects were interviewed, face-to-face, at home; the lifetime prevalence was 1.4% (0.9% males and 2% females). The majority of attempters were 26-55 years of age, married, more highly educated, female, retired, and lived in urban areas. Many of the attempters (45.3%) reported at least one psychiatric disorder during their lifetime; major depressive disorder (22%), panic disorder (6.3%), and obsessive compulsive disorder (6%) was the most common. Because less than half of suicidal attempters reported a psychiatric disorder, the existence of other pathways to suicide may be important foci for prevention. Many of the demographic correlates of suicidal behavior in Iran are very similar to those seen in Western cutlures; however, the sociodemographic factors such as few working women and very low levels of divorce is quite different to that of Western populations.     

Ethanol state-dependent memory: involvement of dorsal hippocampal muscarinic and nicotinic receptors

In the present study, the effects of bilateral injections of cholinergic agents into the hippocampal CA1 regions (intra-CA1) on ethanol state-dependent memory were examined in mice. A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Pre-training intraperitoneal injection (i.p.) of ethanol (0.25, 0.5 and 1 g/kg) dose dependently induced impairment of memory retention. Pre-test administration of ethanol (0.5 and 1 g/kg, i.p.) induced state-dependent retrieval of the memory acquired under pre-training ethanol (1 g/kg, i.p.) influence. Pre-test intra-CA1 injection of physostigmine (2.5 and 5 μg/mouse, intra-CA1) or nicotine (0.3 and 0.5 μg/mouse, intra-CA1) improved pre-training ethanol (1 g/kg)-induced retrieval impairment. Moreover, pre-test administration of physostigmine (2.5 and 5 μg/mouse, intra-CA1) or nicotine (0.3 and 0.5 μg/mouse, intra-CA1) with an ineffective dose of ethanol (0.25 g/kg) significantly restored the retrieval and induced ethanol state-dependent memory. Pre-test intra-CA1 injection of the muscarinic receptor antagonist, atropine (4 and 8 μg/mouse, intra-CA1) or the nicotinic receptor antagonist, mecamylamine (2 and 4 μg/mouse, intra-CA1) 5 min before the administration of ethanol (1 g/kg, i.p.) dose dependently inhibited ethanol state-dependent memory. Pre-test intra-CA1 administration of physostigmine (0.5, 2.5 and 5 μg/mouse), atropine (2, 4 and 8 μg/mouse), nicotine (0.1, 0.3 and 0.5 μg/mouse) or mecamylamine (1, 2 and 4 μg/mouse) alone cannot affect memory retention. These findings implicate the involvement of a dorsal hippocampal cholinergic mechanism in ethanol state-dependent memory and also it can be concluded that there may be a cross-state dependency between ethanol and acetylcholine.     

N-Methyl-D-aspartate receptors in the ventral tegmental area are involved in retrieval of inhibitory avoidance memory by nicotine

The interaction of opiate, cholinergic, glutamatergic and (possibly) dopaminergic inputs in the ventral tegmental area (VTA) influencing a learned behavior is certainly a topic of great interest. In the present study, the effect of intra-VTA administration of N-methyl-d-aspartate (NMDA) receptor agents on nicotine's effect in morphine state-dependent learning was investigated. An inhibitory avoidance (IA) task was used for memory assessment in male Wistar rats. Subcutaneous (s.c.) administration of morphine (5 and 7.5mg/kg) immediately after training decreased IA response on the test day, which was reinstated by pre-test administration of the same doses of the opioid; this is known as state-dependency. Moreover, pre-test administration of nicotine (0.2, 0.4 and 0.6 mg/kg, s.c.) also reversed the decrease in IA response because of post-training morphine (5mg/kg). Here, we also show that when infused into the VTA before testing, NMDA (0.01 and 0.1 microg/rat) reverse the post-training morphine effect on memory. In addition, the sub-effective doses of NMDA (0.0001 and 0.001 microg/rat) in combination with a low dose of nicotine (0.1mg/kg) which had no effects by themselves, synergistically improved retrieval of IA memory on the test day. In contrast, pre-test administration of a competitive NMDA receptor antagonist D-AP5 (0.5, 1 and 2 microg/rat) which had no effect alone prevented the nicotine reversal of morphine effect on memory. Our data indicate that NMDA receptors in the VTA are involved in the reversing effect of nicotine on morphine induced state-dependency.     

Influence of intracerebroventricular administration of dopaminergic drugs on morphine state-dependent memory in the step-down passive avoidance test

The effects of dopaminergic drugs on morphine state-dependent memory of passive avoidance task were examined in mice. Pre-training administration of morphine (5mg/kg) led to state-dependent learning with impaired memory retrieval on the test day which was reversed by pre-test administration of the same dose of the opiate. The pre-test intracerebroventricular (i.c.v.) administration of the dopamine D1 receptor agonist (SKF38393), dopamine D2 receptor agonist (quinpirole) and dopamine D2 receptor antagonist (sulpiride) not only reversed the effect of pre-training morphine treatment, but also increased this action of the drug. Furthermore, the pre-test i.c.v. administration of dopamine D1 receptor antagonist (SCH23390) prevented the restoration of memory by morphine. In conclusion, the morphine-induced recovery of memory, on the test day, seems to be induced, at least in part, through dopamine receptors.     

Involvement of dorsal hippocampal α-adrenergic receptors in the effect of scopolamine on memory retrieval in inhibitory avoidance task

The present study evaluated the possible role of α-adrenergic receptors of the dorsal hippocampus on scopolamine-induced amnesia and scopolamine state-dependent memory in adult male Wistar rats. The animals were bilaterally implanted with chronic cannulae in the CA1 regions of the dorsal hippocampus, trained in a step-through type inhibitory avoidance task, and tested 24 h after training to measure step-through latency. Results indicate that post-training or pre-test intra-CA1 administration of scopolamine (1 and 2 μg/rat) dose-dependently reduced the step-through latency, showing an amnestic response. Amnesia produced by post-training scopolamine (2 μg/rat) was reversed by pre-test administration of the scopolamine that is due to a state-dependent effect. Interestingly, pre-test intra-CA1 microinjection of α1-adrenergic agonist, phenylephrine (1 and 2 μg/rat) or α2-adrenergic agonist, clonidine improved post-training scopolamine (2 μg/rat)-induced retrieval impairment. Furthermore, pre-test intra-CA1 microinjection of phenylephrine (0.25, 0.5 and 1 μg/rat) or clonidine (0.25, 0.5 and 1 μg/rat) with an ineffective dose of scopolamine (0.25 μg/rat), synergistically improved memory performance impaired by post-training scopolamine. On the other hand, pre-test injection of α1-receptors antagonist prazosin (1 and 2 μg/rat) or α2-receptors antagonist yohimbine (1 and 2 μg/rat) prevented the restoration of memory by pre-test scopolamine. It is important to note that pre-test intra-CA1 administration of the same doses of prazosin or yohimbine, alone did not affect memory retrieval. These results suggest that α1- and α2-adrenergic receptors of the dorsal hippocampal CA1 regions may play an important role in scopolamine-induced amnesia and scopolamine state-dependent memory.     

The effects of adenosine receptor agonists and antagonists on morphine state-dependent memory of passive avoidance

Pretraining administration of morphine (5 mg/kg, intraperitonically) in a step-down passive avoidance task led to state-dependent learning with impaired retrieval on the test day that was dose-dependently restored by pretest administration of morphine (0.5, 1, 3, and 5 mg/kg). This restoration was reversible by pretest naloxone administration. Pretest administration of adenosine receptor antagonists theophylline or 8-phenyltheophylline (8-PT) did not alter morphine-induced amnesia. However, both the antagonists inhibited the restoration of memory by pretest morphine (5 mg/kg). Adenosine A(1) receptor agonists N(6)-cyclohexyladenosine (CHA) or N(6)-phenylisopropyladenosine (R-PIA) only at the higher doses used, and adenosine A(2) receptor agonist 5'-N-ethylcarboxaminoadenosine (NECA), at all doses used, decreased morphine-induced amnesia in a dose-dependent manner. Pretest administration of low doses of CHA, R-PIA, or NECA significantly showed additive effects with low dose pretest morphine (1 mg/kg) in restoring memory. The promnestic effects of high-dose CHA and R-PIA were inhibited by theophylline or 8-PT but not by naloxone. The additive effects of low-dose CHA or R-PIA and morphine were inhibited by theophylline, 8-PT, or a higher dose of naloxone. The promnestic effect of NECA and its additive effect with low-dose morphine were both inhibited by theophylline and naloxone but not by 8-PT. It is concluded that activation of the adenosinergic system, through both A(1) and A(2) receptors, can reverse morphine-induced amnesia and is involved in morphine state of memory.     

Activation of cannabinoid CB1 receptors in the central amygdala impairs inhibitory avoidance memory consolidation via NMDA receptors

In the present study, we investigated the influence of bilateral intra-central amygdala (intra-CeA) microinjections of N-methyl-d-aspartate (NMDA) receptor agents on amnesia induced by a cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA). This study used a step-through inhibitory (passive) avoidance task to assess memory in adult male Wistar rats. The results showed that intra-CeA administration of ACPA (2 ng/rat) immediately after training decreased inhibitory avoidance (IA) memory consolidation as evidenced by a decrease in step-through latency on the test day, which was suggestive of drug-induced amnesia. Post-training intra-CeA microinjections of NMDA (0.0001, 0.001 and 0.01 μg/rat) did not affect IA memory consolidation. However co-administration of NMDA with ACPA (2 ng/rat) prevented the impairment of IA memory consolidation that was induced by ACPA. Although post-training intra-CeA administration of the NMDA receptor antagonist, d-(−)-2-amino-5-phosphonopentanoic acid (d-AP5; 0.01, 0.05 and 0.1 μg/rat) alone had no effect, its co-administration with an ineffective dose of ACPA (1 ng/rat) impaired IA memory consolidation. Post-training intra-CeA microinjection of an ineffective dose of d-AP5 (0.01 μg/rat) prevented an NMDA response to the impaired effect of ACPA. These results suggest that amnesia induced by intra-CeA administration of ACPA is at least partly mediated through an NMDA receptor mechanism in the Ce-A.     

Nicotinic acetylcholine receptors of the ventral tegmental area are involved in mediating morphine-state-dependent learning

In the present study, the possible role of nicotinic acetylcholine (nACh) receptors of the ventral tegmental area (VTA) on morphine-state-dependent learning was studied in adult male Wistar rats. As a model of memory, a step-through type passive avoidance task was used. All animals were bilaterally implanted with chronic cannulae in the VTA, trained using a 1 mA foot shock, and tested 24 h after training to measure step-through latency. Post-training subcutaneous (s.c.) injection of morphine (0.5–5 mg/kg) dose-dependently reduced the step-through latency, showing morphine-induced amnesia. Amnesia induced by post-training morphine was significantly reversed by pre-test administration of morphine (2.5–5 mg/kg, s.c.) and induced morphine-state-dependent learning. Pre-test injection of nicotine (0.25–1 μg/rat) into the VTA plus an ineffective dose of morphine (0.5 mg/kg) significantly restored the memory retrieval. It should be noted that pre-test intra-VTA injection of the same doses of nicotine (0.25–1 μg/rat) alone cannot affect memory retention. Furthermore, pre-test intra-VTA injection of the nicotinic acetylcholine receptor antagonist, mecamylamine (1–3 μg/rat) 5 min before the administration of morphine (5 mg/kg, s.c.) dose-dependently inhibited morphine-state-dependent learning. Pre-test injection of the higher dose of mecamylamine (3 μg/rat) into the VTA by itself decreased the step-through latency and induced amnesia. On the other hand, mecamylamine (0.5 and 1 μg/rat, intra-VTA) reversed the effect of nicotine on morphine response. The results indicate that nACh receptors in the VTA participate in the modulation of morphine-induced recovery of memory, on the test day.