Biological Science

In the present study, we investigated effects of intra-central amygdala (intra-CeA) administrations of a ␤1-receptor agonist and antagonist, isoprenaline (isoproterenol) and atenolol respectively, on state-dependent memory induced by a cannabioid agonist, WIN55,212-2. This study used a step-through inhibitory avoidance task to assess memory in male Wistar rats. The results showed that post-training intra-CeA administrations of different doses of WIN55,212-2 (0.01, 0.05, 0.1 and 0.25 g/rat) decreased memory as revealed by a decrease in memory retrieval on the test day. The decrease in retrieval induced by post-training WIN55,212-2 (0.25 g/rat) was reversed by pre-test administration of the same dose of the drug, which was suggestive of drug-induced state-dependent memory. Although pre-test intra-CeA administrations of isoprenaline (0.01, 0.025 and 0.05 g/rat) alone had no effect, its co-administrations at doses of 0.025 and 0.05 g/rat with an ineffective dose of WIN55,212-2 (0.1 g/rat) restored memory retrieval that impaired by post-training WIN55,212-2 (0.25 g/rat). The results also showed that pre-test intra-CeA administrations of atenolol (0.01, 0.05 and 0.1 g/rat) alone had no effect, but at dose of 0.1 g/rat disrupted state-dependent memory induced by WIN55,212-2. Moreover, the improving effect of isoprenaline (0.025 g/rat) on retrieval of state-dependent memory induced by WIN55,212-2 (0.1 g/rat) was prevented by intra-CeA co-injections of atenolol. Taken together, our results suggest that the CeA may be potentially critical for statedependent memory induced by WIN55,212-2 and the ␤1-noradrenergic receptor mechanism(s) interact with the cannabinergic system in the modulation of this kind of memory in the CeA.

In the present study, we investigated the influence of intra-medial septum (intra-MS) injections of dopamine D1 receptor agents on amnesia induced by intra-CA1 injections of a muscarinic acetylcholine receptor antagonist, scopolamine. This study used a step-through inhibitory (passive) avoidance task to assess memory in adult male Wistar rats. The results showed that in the animals that received posttraining intra-MS injections of saline, intra-CA1 administrations of scopolamine (0.75, 1, and 2 g/rat) 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-MS injections of a dopamine D1 receptor agonist, SKF38393 at doses of 0.1, 0.15, and 0.3 g/rat had no effect, but at dose of 0.5 g/rat impaired IA memory consolidation. Interestingly, intra-MS injections of SKF38393 (0.15, 0.3 and 0.5 g/rat) significantly prevented amnesia induced by intra-CA1 injections of scopolamine (1 g/rat). Intra-MS injections of a dopamine D1 receptor antagonist, SCH23390 (0.5 and 0.75 g/rat) by itself impaired IA memory consolidation, and also at dose of 0.75 g/rat increased amnesia induced by intra-CA1 administrations of an ineffective dose of scopolamine (0.5 g/rat). Post-training intra-MS injections of ineffective doses of SCH23390 (0.1, 0.3 and 0.5 g/rat) prevented an effective dose of SKF38393 response to the impaired effect of scopolamine. These results suggest that dopamine D1 receptors in the MS via projection neurons to the hippocampus affect impairment of memory consolidation induced by intra-CA injections of scopolamine.

In the present study, the effects of intra-basolateral amygdala (BLA) injection of GABA A receptor agonist and antagonist on morphineinduced conditioned place preference (CPP) in male Wistar rats have been investigated. Subcutaneous (s.c.) administration of different doses of morphine sulfate (1 -9 mg/kg) produced a dose-dependent CPP. Using a 3-day schedule of conditioning, it was found that the GABA A receptor agonist, muscimol (0.125, 0.25 and 0.5 Ag/rat) or the GABA A receptor antagonist, bicuculline (0.125, 0.25 and 0.5 Ag/rat), did not produce a significant place preference or place aversion. Intra-BLA administration of muscimol (0.25 and 0.5 Ag/rat) decreased the acquisition of CPP induced by morphine (6 mg/kg). On the other hand, intra-BLA injection of bicuculline (0.25 and 0.5 Ag/rat) in combination with an ineffective dose of morphine (1 mg/kg) elicited a significant CPP. The response of different doses of muscimol was attenuated by bicuculline (0.125 and 0.25 Ag/rat). Furthermore, intra-BLA administration of bicuculline but not muscimol before testing significantly decreased the expression of morphine (6 mg/kg)-induced place preference. The administration of the higher doses of bicuculline (0.25 and 0.5 Ag/rat) during acquisition and the higher dose of muscimol (2 Ag/rat) on the test day decreased the locomotor activity of the animals on the testing phase. It can be concluded that GABA A receptors in the amygdala are involved in morphine reward. D

1. Repeated administration of psychostimulants and opioid receptor agonists elicits a progressive enhancement of drug-induced behavioural responses, a phenomenon termed behavioural sensitization. These changes in behaviour may reflect plastic changes requiring regulation of -amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptor function.

The effects of dopaminergic drugs on the inhibitory avoidance memory affected by lithium were examined in the Naval Medical Research Institute (NMRI) mice using a single-trial step-down inhibitory (passive) avoidance task. The results showed that post-training administration of lithium (10 mg/kg, i.p.) decreased the step-down latency on the test day, which was fully or partly reversed by pre-test administration of the same dose of the drug; suggesting state-dependent learning induced by lithium. Our results also showed that pre-test (i.p.) administration of the dopamine D1 receptor agonist SKF38393 and the dopamine D2 receptor agonist quinpirole by themselves and in combination with ineffective doses of lithium (0.3, 0.6 and 1.25 mg/kg) reversed the decrease of the step-down latency induced by post-training lithium. In contrast, pre-test administration of the dopamine D1 receptor antagonist SCH23390 (0.025, 0.05 and 0.1 mg/kg, i.p.) and the dopamine D2 receptor antagonist sulpiride (6.25 and 12.5 mg/kg, i.p.) alone or in combination with pre-test lithium (10 mg/kg), did not significantly alter the step-down latency on the test day, except for a higher dose of sulpiride (25 mg/kg) which by itself increased the step-down latency. Furthermore, pre-test administration of a lower dose of sulpiride (3 mg/kg) in combination with ineffective doses of lithium (03, 0.6 and 1.25 mg/kg) also reversed the decrease in the step-down latency induced by post-training lithium. In conclusion, the dopamine D1 and D2 receptor mechanism(s) may be involved, at least partly, in the effect of lithium on retrieval of the inhibitory avoidance memory influenced by the drug.

In the present study, effects of lithium chloride (LiCl) on morphine induced state-dependent memory of passive avoidance task were examined in mice. One-trial step-down paradigm was used for the assessment of memory retention in adult male NMRI mice. Administration of morphine (5 mg/kg) subcutaneously (s.c.) 30 min before training or testing induced impairment of memory performance. Injection of the same dose of the drug 30 min before testing restored memory retention impaired under pre-training morphine effect. Intraperitoneal (i.p.) injection of lithium, 60 min before training or prior to testing also impaired memory performance. Under the pre-training of morphine, the response of the opioid was restored when animals received LiCl (80 and 160 mg/kg) as pre-test injection. Pre-training administration of lower dose of lithium (20 mg/kg), but not the higher doses of the drug (80 and 160 mg/kg) impaired memory retention in passive avoidance test. LiCl-induced impairment of memory retention was restored by pre-test administration of morphine. In the animals receiving pre-training morphine, combined pre-test morphine and LiCl administration increased the restoration of memory by the opioid. It can be concluded that there may be a cross-state dependency between morphine and lithium. D

These experiments examined the effects of pre-test intra dorsal hippocampus (intra-CA1) administration of GABAA receptor agonist and antagonist, muscimol and bicuculline respectively, on state-dependent learning induced by lithium. Male NMRI mice were trained in a one-trial step-down inhibitory avoidance task, and immediately after training they received IP injections of either saline (10 mL/kg) or lithium (10 mg/kg). The animals were tested for step-down latency, as an index of inhibitory avoidance memory, 24 h after the training. The results showed that lithium (10 mg/kg) induced state-dependent learning. Although the decrease of step down latency due to post-training lithium (10 mg/kg) was not fully reversed by a lower dose of lithium (5 mg/kg) but pre-test intra-CA1 injection of bicuculline (0.25 μg/mouse) increased the effect of the lower dose of lithium. Pre-test intra-CA1 injection of muscimol (0.05 μg/mouse) by itself reversed the decrease of step-down latency induced by pos...

Calcium/calmodulin-dependent protein kinase II (CaMKII) which is highly expressed in the hippocampus is known to play a pivotal role in reward-related memories and morphine dependence. In the present study, repeated morphine injections once daily for 7 days was done to induce morphine tolerance in male Wistar rats, after which gene expression profile of α-isoform of CaMKII (CaMKIIα) in the hippocampus was evaluated upon discontinuation of morphine injection over 21 days of morphine withdrawal. Control groups received saline for 7 consecutive days. For gene expression study, rats' brains were removed and the hippocampus was dissected in separate groups on days 1, 3, 7, 14, and 21 since discontinuation of of morphine injection. A semi-quantitative RT-PCR method was used to evaluate the gene expression profile. Tolerance to morphine was verified by a significant decrease in morphine analgesia in a hotplate test on day 8 (one day after the final repeated morphine injections). Result...

We investigated the role of ATP-sensitive potassium channels and L-type calcium channels in morphine-induced hyperalgesia after nociceptive sensitization. We used a hotplate apparatus to assess pain behavior in male NMRI mice. Nociceptive sensitization was induced by three days injection of morphine and five days of drug free. On day 9 of the schedule, pain behavior test was performed for evaluating the effects of morphine by itself and along with nimodipine, a blocker of L-type calcium channels and diazoxide, an opener of ATP-sensitive potassium channels. All drugs were injected through an intraperitoneal route. The results showed that morphine (7.5, 10 and 15 mg/kg) induced analgesia in normal mice, which was prevented by naloxone (1 mg/kg). After nociceptive sensitization, analgesic effect of morphine (10 and 15 mg/kg) was significantly decreased in sensitized mice. The results showed that nimodipine (2.5, 5, 10 and 20 mg/kg) had no significant effect on pain behavior test in eit...

Introduction: In this study, we investigated the role of N-Methyl-D-Aspartate (NMDA) receptors in the ventral hippocampus (VH) and their possible interactions with GABA A system on anxiety-like behaviors. Methods: We used an elevated-plus maze test (EPM) to assess anxiety-like behaviors and locomotor activity in male Wistar rats. Results: The results showed that intra-VH infusions of different doses of NMDA (0.25 and 0.5 µg/rat) increased locomotor activity, and also induced anxiolytic-like behaviors, as revealed by a tendency to increase percentage of open arm time (%OAT), and a significant increase in percentage of open arm entries (%OAE). The results also showed that intra-VH infusions of muscimol (0.5 and 1 µg/rat) or bicuculline (0.5 and 1 µg/rat) did not significantly affect anxiety-like behaviors, but bicuculline at dose of 1 µg/rat increased locomotor activity. Intra-VH co-infusions of muscimol (0.5 µg/rat) along with low doses of NMDA (0.0625 and 0.125 µg/rat) showed a tend...

Backgrounds: The amnesic effect of morphine is well known in the laboratory animals. But, it is unclear that morphine at what times can exactly affect different phases of memory, including acquisition, consolidation, and retrieval. Therefore, we investigated the time pro le of morphine's amnesic effect on passive (inhibitory) avoidance learning and memory in male Wistar rats.

The influence of repeated administration of dopamine receptor agents on the effect of lithium on lithium-induced state-dependent learning was examined in mice. Immediate post-training intraperitoneal (i.p.) administrations of lithium (10 and 20 m/kg) decreased the step-down latency of a single-trial inhibitory avoidance task. This was fully or partly reversed by pre-test administration of the same doses of the drug, with maximum response at the dose of 10 mg/kg, suggesting state-dependent learning was induced by lithium. Here, it has also been shown that repeated intracerebroventricular administrations of a mixed D1/D2 dopamine receptors agonist apomorphine (once daily injections of 0.5 μg/mouse for three consecutive days followed by five days of no drug treatment) increased the effect of lower doses of pre-test lithium (1.25, 2.5 and 5 mg/kg, i.p.) on the reinstatement of the step-down latency decreased by post-training lithium (10 mg/kg). On the contrary, not only repeated administrations of the dopamine D1 receptor antagonist SCH 23390 (0.5 and 1 μg/mouse) but also the dopamine D2 receptor antagonist sulpiride (0.3 and 1 μg/mouse) disrupted the state-dependent learning induced by lithium. These results suggest that state-dependent learning induced by lithium may be altered by repeated pretreatment of dopamine receptor agents.

In the present study interactions between analgesic effect of morphine with blockade of ATP-sensitive potassium channels and L-type calcium channels were investigated in alloxan-induced diabetic mice. A hot plate test was used to assess analgesic effect of drugs in adult male NMRI mice. All drugs were injected through an intraperitoneal route. A diabetic mouse model was established by injections of alloxan for three consecutive days. Seventy-two hours after the final injection, mice with a blood glucose level higher than 11.1 mmol/l were considered as diabetic. The results showed that morphine at doses of 10 and 15 mg/kg induced analgesia in both non-diabetic and diabetic mice, but the analgesic effect of morphine at dose of 7.5 mg/kg was decreased in diabetic mice. Injections of an ATP-sensitive potassium channel blocker, glibenclamide (4, 8, 12, 20 mg/kg) had no effect in non-diabetic mice, while at doses of 12 and 20 mg/kg induced analgesia in diabetic mice. Blockade of L-type calcium channels with nimodipine at different doses (2.5, 5, 10 and 20 mg/kg) was ineffective in non-diabetic mice, but at dose of 20 mg/kg induced analgesia in diabetic mice. Co-administrations of glibenclamide (20 mg/kg) or nimodipine (20 mg/kg) along with different doses of morphine (5, 7.5 and 10 mg/kg) improved the analgesic effect of the later drug in diabetic mice. According to the present results, it is possible that diabetes via affecting the potassium and calcium channels in the pain pathways may alter processing of pain in the peripheral and central nervous system.