sch-23390 and Amnesia

In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocampal CA1 regions (intra-CA1) on harmaline-induced amnesia were examined in male mice. A one-trial step-down passive avoidance task was used for the assessment of memory retention in adult male mice. Pre-training intra-peritoneal (i.p.) administration of harmaline (1 mg/kg) induced impairment of memory retention. Moreover, intra-CA1 administration of dopamine D1 receptor antagonist, SCH23390 (0.02 μg/mouse), dopamine D1 receptor agonist, SKF38393 (0.5 μg/mouse), dopamine D2 receptor antagonist, sulpiride (1 μg/mouse) and dopamine D2 receptor agonist, quinpirole (0.25 and 0.5 μg/mouse) suppressed the learning of a single-trial passive avoidance task. Also, pre-training intra-CA1 injection of subthreshold doses of SCH23390 (0.001 μg/mouse) or sulpiride (0.25 μg/mouse) with the administration of harmaline (1 mg/kg, i.p.) reversed impairment of memory formation. However, pre-training intra-CA1 injection of SKF38393 (0.1 μg/mouse) or quinpirole (0.1 μg/mouse) increased pre-training harmaline (0.25 and 0.5 mg/kg, i.p.)-induced retrieval impairment. Moreover, SKF Ca blocker (SKF) (0.01 μg/mouse) decrease the amnesia induced by harmaline (1 mg/kg), while co-administration of SKF (0.01 μg/mouse)/sulpiride (0.25 μg/mouse) or SCH23390 (0.001 μg/mouse)/sulpiride (0.25 μg/mouse) potentiate amnesia caused by harmaline. These findings implicate the involvement of CA1 dopaminergic mechanism in harmaline-induced impairment of memory acquisition.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Amnesia; Animals; Avoidance Learning; Benzazepines; CA1 Region, Hippocampal; Dopamine; Dopamine Agonists; Dopamine Antagonists; Harmaline; Male; Memory; Mice; Monoamine Oxidase Inhibitors; Receptors, Dopamine D1; Receptors, Dopamine D2; Sulpiride

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 post-training intra-MS injections of saline, intra-CA1 administrations of scopolamine (0.75, 1, and 2 μg/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 μg/rat had no effect, but at dose of 0.5 μg/rat impaired IA memory consolidation. Interestingly, intra-MS injections of SKF38393 (0.15, 0.3 and 0.5 μg/rat) significantly prevented amnesia induced by intra-CA1 injections of scopolamine (1 μg/rat). Intra-MS injections of a dopamine D1 receptor antagonist, SCH23390 (0.5 and 0.75 μg/rat) by itself impaired IA memory consolidation, and also at dose of 0.75 μg/rat increased amnesia induced by intra-CA1 administrations of an ineffective dose of scopolamine (0.5 μg/rat). Post-training intra-MS injections of ineffective doses of SCH23390 (0.1, 0.3 and 0.5 μg/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.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Amnesia; Analysis of Variance; Animals; Avoidance Learning; Benzazepines; Disease Models, Animal; Dopamine Agonists; Dopamine Antagonists; Dose-Response Relationship, Drug; Drug Interactions; Hippocampus; Inhibition, Psychological; Male; Microinjections; Rats; Rats, Wistar; Receptors, Dopamine D1; Scopolamine; Septum of Brain

Changes in the effects of D1-receptor activation and blockade on the amnesia induced by delay in unsafe compartment in mice after forced swimming were studied using conditioned passive avoidance test. The most pronounced antiamnestic effects in mice with behavioral despair reaction were observed after administration of D1 receptor antagonist SCH23390, while D1 receptor antagonist SKF38393 was most effective in mice without preliminary stimulation.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Amnesia; Animals; Avoidance Learning; Benzazepines; Depressive Disorder; Dopamine Agonists; Dopamine Antagonists; Injections, Intraperitoneal; Male; Mice; Mice, Inbred C57BL; Receptors, Dopamine D1; Stress, Physiological; Swimming

In the present study, the effects of morphine treatment upon reduction of memory consolidation by post-training administration of the non-selective cannabinoid CB(1)/CB(2) receptor agonist, WIN55,212-2, into the dorsal hippocampus (intra-CA1) have been investigated in rats. Step-through inhibitory avoidance apparatus was used to test memory retrieval, which was made of two white and dark compartments. In training day, electric shocks were delivered to the grid floor of the dark compartment. On the test day, the animal was placed in the white compartment and allowed to enter the dark compartment. The latency with which the animal crossed into the dark compartment was recorded as memory retrieval. Morphine was injected subcutaneously (S.C.), once daily for three days, followed by a five day morphine-free period before training. Bilateral post-training intra-CA1 infusions of WIN55,212-2 (0.25 and 0.5 μg/rat) shortened the step-through latency, which suggested impaired memory consolidation. The deleterious effect of WIN55,212-2 (0.5 μg/rat) was prevented in rats previously injected with morphine (10 mg/kg/day × 3 days, S.C.). Prevention of the WIN55,212-2-induced amnesic-like effect was counteracted by the mu-receptor antagonist, naloxone, and the dopamine D(2) receptor antagonist, sulpiride, but not by the D(1) receptor antagonist, SCH 23390, when administered prior to each morphine injection. The results have suggested that subchronic morphine treatment may cause mu-opioid and D(2) receptor sensitization, which in turn prevents impairment of memory consolidation induced by WIN55,212-2.

Topics: Amnesia; Analgesics; Animals; Avoidance Learning; Benzazepines; Benzoxazines; CA1 Region, Hippocampal; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Male; Memory; Memory Disorders; Morphine; Morpholines; Naloxone; Naphthalenes; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Receptors, Dopamine D1; Receptors, Opioid, mu; Sulpiride; Time Factors

The aim of the present study was to investigate the existence of possible functional correlation between GABA-A and dopamine (DA) receptors of the dorsal hippocampus and the ventral tegmental area (VTA) in passive avoidance learning. Two guide cannulas were stereotaxically implanted in the CA1 region of the dorsal hippocampus and the VTA of male Wistar rats. In order to measure memory retrieval, the animals were trained in a step-through type passive avoidance task and tested 24 h after training. Post-training intra-CA1 administration of a GABA-A receptor agonist, muscimol (0.01-0.02 μg/rat) dose-dependently impaired memory retrieval. Post-training intra-VTA administration of SCH23390 (a dopamine D1 receptor antagonist; 0.1-0.8 μg/rat) or sulpiride (a D2 receptor antagonist; 0.5-1.5 μg/rat) decreased the inhibitory effect of muscimol (0.02 μg/rat, intra-CA1) on memory retrieval. Intra-VTA administration of the same doses of SCH23390, but not sulpiride, decreased the step-through latencies. On the other hand, post-training administration of muscimol (0.02 μg/rat) into the VTA inhibited memory retrieval. The administration of SCH23390 (0.01-0.2 μg/rat) or sulpiride (0.1-1 μg/rat) into the CA1 region, immediately after training, had no effect on memory retrieval. Furthermore, the amnesic effect of intra-VTA administration of muscimol was significantly decreased by intra-CA1 administration of sulpiride (0.5 and 1 μg/rat, intra-CA1), but not SCH23390. The practical conclusion is that the relationship between the hippocampus and the VTA may regulate memory formation in passive avoidance learning. Also, the correlation between the hippocampus and VTA by a dopaminergic system may be involved in mediating muscimol-induced amnesia.

Topics: Amnesia; Animals; Avoidance Learning; Benzazepines; Dopamine Antagonists; Dopaminergic Neurons; Dose-Response Relationship, Drug; Drug Interactions; GABA-A Receptor Agonists; GABAergic Neurons; Hippocampus; Male; Mental Recall; Microinjections; Muscimol; Rats; Rats, Wistar; Sulpiride; Ventral Tegmental Area

Ingestion of harmane and other alkaloids derived from plant Peganum harmala has been shown to elicit profound behavioural and toxic effects in humans, including hallucinations, excitation, feelings of elation, and euphoria. These alkaloids in the high doses can cause a toxic syndrome characterized by tremors and convulsions. Harmane has also been shown to act on a variety of receptor systems in the mammalian brain, including those for serotonin, dopamine and benzodiazepines. In animals, it has been reported to affect short and long term memory. In the present study, effects of dopamine D1 and D2 receptor antagonists on the harmane (HA)-induced amnesia and exploratory behaviors were examined in mice. One-trial step-down and hole-board paradigms were used for the assessment of memory retention and exploratory behaviors in adult male NMRI mice respectively. Intraperitoneal (i.p.) administration of HA (5 and 10 mg/kg) immediately after training decreased memory consolidation, while had no effect on anxiety-like behavior. Memory retrieval was not altered by 15- or 30 min pre-testing administration of the D1 (SCH23390, 0.025, 0.05 and 0.1 mg/kg) or D2 (sulpiride 12.5, 25 and 50 mg/kg) receptor antagonists, respectively. In contrast, SCH23390 (0.05 and 0.1 mg/kg) or sulpiride (25 and 50 mg/kg) pre-test administration fully reversed HA-induced impairment of memory consolidation. Finally, neither D1 nor D2 receptor blockade affected exploratory behaviors in the hole-board paradigm. Altogether, these findings strongly suggest an involvement of D1 and D2 receptors modulation in the HA-induced impairment of memory consolidation.

Topics: Amnesia; Animals; Avoidance Learning; Benzazepines; Dopamine D2 Receptor Antagonists; Exploratory Behavior; Harmine; Male; Mice; Pilot Projects; Reaction Time; Receptors, Dopamine D1; Receptors, Dopamine D2

Repeated administration of certain drugs could result in an enhancement of the behavioral effects of those drugs. In the present study, the effect of repeated administration of histamine on amnesia induced by post-training administration of the drug was examined.. A single trial step-down inhibitory (passive) avoidance task was used for memory assessment in male NMRI mice.. The results showed that post-training administration of different doses of histamine (5, 10, and 20 microg/mouse, i.c.v.) decreased the step-down latency on the test day. Repeated pretreatment of histamine (10 and 20 microg/mouse) for three days followed by five days of no drug treatment prevented amnesia due to post-training histamine (20 microg/mouse). In contrast, repeated administration of histamine H1 receptor antagonist, pyrilamine (5, 10, and 20 mg/kg) or histamine H2 receptor antagonist, ranitidine (12.5 and 25 mg/kg) 10 minutes prior to histamine injections, decreased the effect of repeated histamine administration. Moreover, a similar pattern was seen in animals which received dopamine D1 receptor antagonist, SCH 23390 (0.025, 0.5, and 1 mg/kg) or dopamine D2 receptor antagonist, sulpiride (0.2, 1, and 5 mg/kg) 10 minutes prior to histamine injections during the repeated pretreatment.. The results indicated that both the histamine and dopamine receptor mechanisms may be involved in the effects of repeated pretreatment of histamine on drug induced amnesia.

Topics: Amnesia; Analysis of Variance; Animals; Avoidance Learning; Behavior, Animal; Benzazepines; Disease Models, Animal; Dopamine Antagonists; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Administration Schedule; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Male; Mice; Mice, Inbred Strains; Probability; Pyrilamine; Random Allocation; Statistics, Nonparametric; Sulpiride