sch-23390 and Memory-Disorders

Topics: Animals; Antidepressive Agents; Aripiprazole; Benzazepines; Biogenic Monoamines; Citalopram; Dizocilpine Maleate; Dopamine Antagonists; Frontal Lobe; Memory Disorders; Piperazines; Pyridines; Rats; Recognition, Psychology; Serotonin Antagonists

Previous researches showed that maternal deprivation (MD) leads to memory deficits that persist until adulthood. The hippocampus, an important brain structure involved in memory processes, receives dopaminergic afferents from other brain areas that modulate memory. Here we demonstrated that MD results in object recognition memory deficits that are reverted by intra-hippocampal stimulation of D1-dopaminergic receptor and peripheral administration of a dopamine precursor. The D1-dopaminergic receptor and peripheral administration of a dopamine precursor also promoted memory persistence in control rats.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Benzazepines; Dopamine; Dopamine Agonists; Dopamine Antagonists; Female; Hippocampus; Male; Maternal Deprivation; Memory; Memory Disorders; Motor Activity; Rats; Rats, Wistar

The objective of this article is to study the role of the dopamine (DA) D1 receptor in the midbrain periaqueductal grey (PAG) on learning and memory in morphine-addicted rats.. DA D1 receptor agonist SKF81297 and D1 receptor antagonist SCH SCH23390 were administrated into the PAG, respectively, and the learning and memory behavioral changes of morphine addicted rats were detected by water maze. Western blot and immunohistochemistry were used to detect glutamate decarboxylase 67 (GAD67) and tyrosine receptor kinase B (TrkB) in PAG.. D1 receptor agonist shortened the latency to platform and increased the number of platform crossings, indicating improved learning and memory ability of morphine addict rat. D1 receptor agonist increased GAD67 expression and decreased TrkB in PAG.. (1) The PAG is involved in the learning and memory changes of the addicted rats; (2) the activation of DA D1 receptor will increase the GAD67, reduce the damage to peripheral neurons, and improve the learning and memory of the addicted rats; and (3) D1 receptor agonists further reduced TrkB expression in morphine-addicted rats, whereas TrkB levels deviated from changes in rat behavior.

Topics: Animals; Benzazepines; Disease Models, Animal; Dopamine Agonists; Dopamine Antagonists; Dose-Response Relationship, Drug; Glutamate Decarboxylase; Learning Disabilities; Male; Maze Learning; Memory Disorders; Morphine; Narcotics; Periaqueductal Gray; Rats; Rats, Wistar; Receptor, trkB; Receptors, Dopamine D1

Emerging evidence suggests that acupuncture could improve cognitive impairment in vascular dementia by enhancing synaptic plasticity in the hippocampus. The purpose of this study is to investigate whether dopamine, a key mediator of synaptic plasticity, is involved in this cognitive improvement.. Vascular dementia model was established by bilateral common carotid arteries occlusion in male Wistar rats. Three days after the operation, animals received acupuncture treatment for 2 weeks, once daily. The D1/D5 receptors antagonist SCH23390 was administered intraperitoneally 15 minutes before each acupuncture treatment. Morris water maze was examined after acupuncture. Long-term potentiation was studied by an electrophysiological technique. Dopamine and metabolites levels were detected by microdialysis and high-performance liquid chromatography from brain tissue. The expression of D1R and D5R was analyzed by immunofluorescence.. Acupuncture remarkably reversed cognitive deficits in 2-vessel occlusion model (2VO) rats, and the acupuncture points Zusanli (ST36) and Baihui (GV20) were confirmed to be the most effective combination. Electrophysiological recording data showed that 2VO-induced impairments of long-term potentiation were prevented by acupuncture. In addition, acupuncture promoted the release of dopamine and its major metabolites in the hippocampus of 2VO rats. The immunofluorescence experiment showed that the decrease of D1R and D5R in hippocampal dentate gyrus region of 2VO rats was reversed by acupuncture. Furthermore, we found that the effects of acupuncture against 2VO-induced impairments in cognition and synaptic plasticity were abolished by SCH23390.. Improvement in cognition and hippocampal synaptic plasticity induced by acupuncture was achieved via activation of D1/D5 receptors in 2VO rats.

Topics: Acupuncture Therapy; Animals; Behavior, Animal; Benzazepines; Dementia, Vascular; Dentate Gyrus; Disease Models, Animal; Dopamine Antagonists; Long-Term Potentiation; Male; Memory Disorders; Rats; Rats, Wistar; Receptors, Dopamine D1; Receptors, Dopamine D5

Different drugs produce different patterns of impairment on delayed matching-to-sample tasks. For example, (+/-)3,4-methylenedioxymethamphetamine (MDMA) produces an increase in proactive interference. That is, subjects are less accurate when they are required to make a response different to the one they made on the immediately previous trial. The current study assessed whether methamphetamine also produces this particular pattern of disruption in delayed matching-to-sample performance in rats. Methamphetamine primarily reduced accuracy on trials where the correct response differed from the one made on the previous trial. Thus methamphetamine, like MDMA and other stimulant-based drugs of abuse, increased proactive interference. This impairment was reduced by prior administration of the dopamine D1 antagonist SCH23390. These results further extend a general conclusion that a range of stimulant-based drugs may disrupt working memory function indirectly via a tendency to repeat previously made responses and that this disruption is related to D1 receptor activity.

Topics: Amphetamine-Related Disorders; Animals; Benzazepines; Central Nervous System Stimulants; Disease Models, Animal; Dopamine Antagonists; Male; Memory Disorders; Memory, Short-Term; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1

Extinction is the learned inhibition of retrieval. Recently it was shown that a brief exposure to a novel environment enhances the extinction of contextual fear in rats, an effect explainable by a synaptic tagging-and-capture process. Here we examine whether this also happens with the extinction of another fear-motivated task, inhibitory avoidance (IA), and whether it depends on dopamine acting on D1 or D5 receptors. Rats were trained first in IA and then in extinction of this task. The retention of extinction was measured 24 h later. A 5-min exposure to a novel environment 30 min before extinction training enhanced its retention. Right after exposure to the novelty, animals were given bilateral intrahippocampal infusions of vehicle (VEH), of the protein synthesis inhibitor anisomycin, of the D1/D5 dopaminergic antagonist SCH23390, of the PKA inhibitor Rp-cAMP or of the PKC inhibitor Gö6976, and of the PKA stimulator Sp-cAMP or of the PKC stimulator PMA. The novelty increased hippocampal dopamine levels and facilitated the extinction, which was inhibited by intrahippocampal protein synthesis inhibitor anisomysin, D1/D5 dopaminerdic antagonist SCH23390, or PKA inhibitor Rp-cAMP and unaffected by PKC inhibitor Gö6976; additionally, the hippocampal infusion of PKA stimulator Sp-cAMP reverts the effect of D1/D5 dopaminergic antagonist SCH 23390, but the infusion of PKC stimulator PMA does not. The results attest to the generality of the novelty effect on fear extinction, suggest that it relies on synaptic tagging and capture, and show that it depends on hippocampal dopamine D1 but not D5 receptors.

Topics: Animals; Anisomycin; Behavior, Animal; Benzazepines; Carbazoles; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dopamine; Extinction, Psychological; Fear; Hippocampus; Learning; Male; Memory; Memory Disorders; Protein Kinase C; Rats; Rats, Wistar; Receptors, Dopamine D1; Receptors, Dopamine D5; Stress, Physiological; Thionucleotides; Time Factors

Accumulating evidence suggests that dysregulation of histone modification is involved in the pathogenesis and/or pathophysiology of psychiatric disorders. However, the abnormalities in histone modification in the animal model of schizophrenia and the efficacy of antipsychotics for such abnormalities remain unclear. Here, we investigated the involvement of histone modification in phencyclidine-induced behavioral abnormalities and the effects of antipsychotics on these abnormalities. After repeated phencyclidine (10 mg/kg) treatment for 14 consecutive days, mice were treated with antipsychotics (clozapine or haloperidol) or the histone deacetylase inhibitor sodium butyrate for 7 d. Repeated phencyclidine treatments induced memory impairment and social deficit in the mice. The acetylation of histone H3 at lysine 9 residues decreased in the prefrontal cortex with phencyclidine treatment, whereas the expression level of histone deacetylase 5 increased. In addition, the phosphorylation of Ca²⁺/calmodulin-dependent protein kinase II in the nucleus decreased in the prefrontal cortex of phencyclidine-treated mice. These behavioral and epigenetic changes in phencyclidine-treated mice were attenuated by clozapine and sodium butyrate but not by haloperidol. The dopamine D1 receptor antagonist SCH-23390 blocked the ameliorating effects of clozapine but not of sodium butyrate. Furthermore, clozapine and sodium butyrate attenuated the decrease in expression level of GABAergic system-related genes in the prefrontal cortex of phencyclidine-treated mice. These findings suggest that the antipsychotic effect of clozapine develops, at least in part, through epigenetic modification by activation of the dopamine D1 receptor in the prefrontal cortex.

Topics: Animals; Antipsychotic Agents; Benzazepines; Butyric Acid; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Clozapine; Dopamine Antagonists; Epigenesis, Genetic; Exploratory Behavior; Hallucinogens; Haloperidol; Histamine Antagonists; Histone Deacetylases; Histones; Male; Memory Disorders; Mice; Mice, Inbred ICR; Phencyclidine; Phencyclidine Abuse; Prefrontal Cortex; Receptors, Dopamine D1

Subanesthetic doses of ketamine have been reported to induce psychotic states that may mimic positive and negative symptoms as well as cognitive and memory deficits similar to those observed in schizophrenia. The cognitive and memory deficits are persistent, and their underlying cellular mechanisms remain unclear.. We sought to investigate the roles of dopamine D1/D5 receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in hippocampal synaptic transmission and spatial memory impairment induced by ketamine.. We examined the effects of subanesthetic ketamine on hippocampal synaptic transmission in freely moving rats. Spatial memory was tested with the Morris water maze. Pretreatment with the D1/D5 receptors antagonist SCH23390 or the AMPA receptors endocytosis interfering peptide Tat-GluR23Y was conducted to examine their capacities to reverse ketamine-induced electrophysiological and behavioral alterations. A series of behavioral observations, including locomotion, prepulse inhibition, and social interaction, were also conducted after ketamine treatment.. Ketamine induced synaptic depression lasting at least 4 h at hippocampal Schaffer collateral-CA1 synapses in freely moving rats and long-term spatial memory impairment. Both the effects were blocked by either SCH23390 or Tat-GluR23Y. Ketamine also elicited transient behavioral changes lasting less than 90 min, such as hyperlocomotion and prepulse inhibition deficits. These changes were ameliorated by SCH23390 but not by Tat-GluR23Y. Rats treated with ketamine showed social withdrawal that was also attenuated by either SCH23390 or Tat-GluR23Y.. Our results indicate that hippocampal synaptic depression is involved in ketamine-induced memory impairment, and this is modulated by D1/D5 receptors activation and AMPA receptors endocytosis.

Topics: Anesthetics, Dissociative; Animals; Benzazepines; CA1 Region, Hippocampal; Dose-Response Relationship, Drug; Ketamine; Male; Maze Learning; Memory Disorders; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Receptors, Dopamine D5; Spatial Behavior; Synaptic Transmission

It is established that stress impairs spatial learning and memory via the hypothalamus-pituitary-adrenal axis response. Dopamine D1 receptors were also shown to be responsible for a stress-induced deficit of working memory. However, whether stress affects the subsequent emotional learning and memory is not elucidated yet. Here, we employed the well-established one-trial step-through task to study the effect of an acute psychological stress (induced by tail hanging for 5, 10, or 20 min) on emotional learning and memory, and the possible mechanisms as well. We demonstrated that tail hanging induced an obvious stress response. Either an acute tail-hanging stress or a single dose of intraperitoneally injected dopamine D1 receptor antagonist (SCH23390) significantly decreased the step-through latency in the one-trial step-through task. However, SCH23390 prevented the acute tail-hanging stress-induced decrease in the step-through latency. In addition, the effects of tail-hanging stress and/or SCH23390 on the changes in step-through latency were not through non-memory factors such as nociceptive perception and motor function. Our data indicate that the hyperactivation of dopamine D1 receptors mediated the stress-induced deficit of emotional learning and memory. This study may have clinical significance given that psychological stress is considered to play a role in susceptibility to some mental diseases such as depression and post-traumatic stress disorder.

Topics: Animals; Benzazepines; Female; Male; Memory; Memory Disorders; Memory, Short-Term; Mice; Receptors, Dopamine D1; Stress, Psychological

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

Marijuana (Cannabis sativa) is one of the most widely used illicit drugs in the world. Its use is associated with impairments in cognitive function. We previously reported that Δ(9)-tetrahydrocannabinol (Δ(9)-THC), the primary psychoactive component of marijuana, impaired spatial working memory in the radial maze task when injected intracortically (IC) into the medial prefrontal cortex (mPFC) of rats. Here, we used this paradigm to evaluate the involvement of prefrontal dopamine receptors in working memory disruption induced by Δ(9)-THC. Intracortical pre-treatment of animals with either the D(1)- or D(2)-like dopamine receptor antagonists SCH 23390 or clozapine, respectively, significantly reduced the number of errors rats made in the radial maze following treatment with Δ(9)-THC also administered intracortically. These results were obtained in the absence of locomotor impairment, as evidenced by the time spent in each arm a rat visited. Our findings suggest that prefrontal dopamine receptors are involved in Δ(9)-THC-induced disruption of spatial working memory. This interaction between the cannabinoid system and dopamine release in the PFC contributes to new directions in research and to treatments for cognitive dysfunctions associated with drug abuse and dependence.

Topics: Animals; Benzazepines; Clozapine; Disease Models, Animal; Dopamine Antagonists; Dronabinol; Male; Maze Learning; Memory Disorders; Prefrontal Cortex; Psychotropic Drugs; Rats; Rats, Wistar

Involvement of the dopamine D1 and D2 receptors in the nucleus accumbens (NAc) with interaction between morphine and nicotine on inhibitory avoidance (IA) memory was investigated. A step-through type of inhibitory avoidance tasks was used to assess memory in male Wistar rats. The results showed that subcutaneous (s.c.) administration of morphine (7.5 mg/kg) after training decreased retrieval of IA memory in the animals when tested 24 h later. Pre-test administration of the same dose of morphine significantly reversed the deficiency in retrieval. The results also showed that pre-test administration of nicotine (0.2 and 0.4 mg/kg, s.c.) by itself mimicked the effect of pre-test morphine, and lower doses of nicotine (0.1 and 0.2 mg/kg) also improved the effect of a low dose of morphine (2.5 mg/kg) on retrieval of IA memory. Pre-test intra-NAc administration of the dopamine D1 receptor antagonist, SCH 23390 (0.001 and 0.01 µg/rat), and the dopamine D2 receptor antagonist, sulpiride (0.5 and 1 µg/rat) caused no significant effects on IA memory by themselves, but both prevented reinstatement of the retrieval of IA memory by the effective dose of nicotine (0.4 mg/kg). It can be concluded that the dopaminergic mechanism(s) in the NAc is a crosslink for the effect of morphine and nicotine on reinstatement of retrieval of IA memory impaired by post-training administration of morphine.

Topics: Animals; Avoidance Learning; Benzazepines; Dopamine Antagonists; Dose-Response Relationship, Drug; Male; Memory Disorders; Morphine; Nicotine; Nicotinic Agonists; Nucleus Accumbens; Rats; Rats, Wistar; Receptors, Dopamine D1; Receptors, Dopamine D2; Sulpiride