Extremely low-frequency electromagnetic field exposure during chronic morphine treatment strengthens downregulation of dopamine D2 receptors in rat dorsal hippocampus after morphine withdrawal

The aim of this study was to investigate the effect of extremely low-frequency electromagnetic field (ELF-EMF) exposure during morphine treatment on dopamine D2 receptor (D2R) density in the rat dorsal hippocampus following withdrawal. Rats were exposed t

抑郁行为及不同抑郁亚型的多巴胺机制研究

The conceptualization of “depression” as a heterogenous disease has been widely accepted by most researchers. However, controlled experiments are rather sparse. To date, most studies demonstrated that animals with helplessness, a widely recognized behavioral index of “depression” also show varied comobidity expressions of other emotional behaviors, such as hightened or lightened anxiety level compared with controls. This means that distinct subtypes of “depression” may exist, in which different neural mechanisms may play roles. The present study aims to explore the possibility of behaviorally categorizing two depressive subtypes, referred as anxious helplessness and non-anxious helplessness, respectively. Then, by using RT-PCR, the dopamine D1, D2, D3 receptors mRNA expressions in medial prefrontal cortex (mPFC) and nucleus accubems (NAc) were quantified. The main findings are described as belows: 1. Uncontrollable shock could readily induce helpless behavior in shocked animals as a whole but with salient individual differences. Prior inescaoable shock induces subsuquent helplessness in approximately 40% shocked animals, while the other animals showed no sign of helpless expression, and were classified as non-helplessness. 2. Among helpless animals, the “subtype” of anxious helpless and non-anxious helpless could be identified according to the anxiety level evaluated by elevated plus maze. 3. D3 receptors mRNA expressions in the mPFC and NAc were increased in stressed animals after uncontrollable shock treatment. At the meanwhile, significant lower expressions of D2 receptors in the mPFC and NAc, and much lower expressions of D1 receptors in the mPFC were found in rats that did not become helpless after stress. In contrast, no significant difference between helpless and control animals was found in D1/D2 receptors mRNA expressions. 4. Based on above mentioned results, the up-regulation of D3 receptors in the mPFC and NAc may reflect a generalized effect of exposure to uncontrollalbe shock. While the down-regulation of D1\D2 receptors in the mPFC and decreased expression of D2 receptors in the NAc may be associated with adaptive or protective mechnisms which protecting animals from helplessness after uncontrollable shock treatment. 5. Futhermore, a significant negative relationship was found between anxiety level and D1 receptors expressions in the mPFC in helpless animals. Compared to the non-anxious helpless and control rats, the D1 receptors mRNA of anxious helpless rats were down-regulation in the mPFC. The present study indicated that the D1 dopamine receptor gene is associated with co-morbid depression and anxiety.

Sexual Behavior Modulates Contextual Fear Memory Through Dopamine D1/D5 Receptors

Traumatic events always lead to aversive emotional memory, i.e., fear memory. In contrast, positive events in daily life such as sex experiences seem to reduce aversive memory after aversive events. Thus, we hypothesized that post-traumatic pleasurable ex

DOPAMINE D2 RECEPTOR MECHANISMS CONTRIBUTE TO AGE-RELATED COGNITIVE DECLINE - THE EFFECTS OF QUINPIROLE ON MEMORY AND MOTOR-PERFORMANCE IN MONKEYS

The D2 dopamine (DA) receptor agonist, quinpirole, was characterized in young adult monkeys, young reserpine-treated monkeys and aged monkeys to assess the contribution of DA to age-related loss of prefrontal cortical (PFC) cognitive function, Monkeys were tested on a delayed response memory task that depends on the PFC, and a fine motor task that taps the functions of the motor cortex, In young adult monkeys, low quinpirole doses impaired performance of the PFC and fine motor tasks, while higher doses improved memory performance and induced dyskinesias and ''hallucinatory-like'' behaviors. The pattern of the quinpirole response in reserpine-treated monkeys suggested that the impairments in delayed response and fine motor performance resulted from drug actions at D2 autoreceptors, while the improvement in delayed response performance, dyskinesias and ''hallucinatory-like'' behaviors resulted from actions at postsynaptic receptors. In aged monkeys, low doses of quinpirole continued to impair fine motor performance, but lost their ability to impair delayed response performance. The magnitude of cognitive improvement and the incidence of ''hallucinatory-like'' behaviors were also reduced in the aged animals, suggesting some loss of postsynaptic D2 receptor function, The pattern of results is consistent with the greater loss of DA from the PFC than from motor areas in aged monkey brain (Goldman-Rakic and Brown, 1981; Wenk et al., 1989), and indicates that DA depletion contributes significantly to age-related cognitive decline.

Electron Beam Surface Treatment. Part I: Surface Hardening of AISI D3 Tool Steel

The effects of electron beam surface hardening treatment on the microstructure and hardness of AISI D3 tool steel have been investigated in this paper. The results showed that the microstructure of the hardened layer consisted of martensite, a dispersion

Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention

An association of the dopamine receptor D4 (DRD4) gene located on chromosome 11p15.5 and attention deficit/hyperactivity disorder (ADHD) has been demonstrated and replicated by multiple investigators. A specific allele [the 7-repeat of a 48-bp variable number of tandem repeats (VNTR) in exon 3] has been proposed as an etiological factor in attentional deficits manifested in some children diagnosed with this disorder. In the current study, we evaluated ADHD subgroups defined by the presence or absence of the 7-repeat allele of the DRD4 gene, using neuropsychological tests with reaction time measures designed to probe attentional networks with neuroanatomical foci in D4-rich brain regions. Despite the same severity of symptoms on parent and teacher ratings for the ADHD subgroups, the average reaction times of the 7-present subgroup showed normal speed and variability of response whereas the average reaction times of the 7-absent subgroup showed the expected abnormalities (slow and variable responses). This was opposite the primary prediction of the study. The 7-present subgroup seemed to be free of some of the neuropsychological abnormalities thought to characterize ADHD.

Evidence of positive selection acting at the human dopamine receptor D4 gene locus

Associations have been reported of the seven-repeat (7R) allele of the human dopamine receptor D4 (DRD4) gene with both attention-deficit/hyperactivity disorder and the personality trait of novelty seeking. This polymorphism occurs in a 48-bp tandem repea

Large Gene Family Expansions and Adaptive Evolution for Odorant and Gustatory Receptors in the Pea Aphid, Acyrthosiphon pisum

Gaining insight into the mechanisms of chemoreception in aphids is of primary importance for both integrative studies on the evolution of host plant specialization and applied research in pest control management because aphids rely on their sense of smell

Improved spatial recognition memory in mice lacking adenosine A(2A) receptors

Adenosine receptors play an important role in learning and memory as their antagonists have been found to facilitate learning and memory in various tasks in rodents. However, few studies have examined the effect of adenosine A(2A) receptor deficiency on c

Long-term depression in rat CA1-subicular synapses depends on the G-protein coupled mACh receptors

The subiculum, which is the primary target of CA1 pyramidal neurons and sending efferent fibres to many brain regions, serves as a hippocampal interface in the neural information processes between hippocampal formation and neocortex. Long-term depression (LTD) is extensively studied in the hippocampus, but not at the CA1-subicular synaptic transmission. Using whole-cell EPSC recordings in the brain slices of young rats, we demonstrated that the pairing protocols of low frequency stimulation (LFS) at 3 Hz and postsynaptic depolarization of -50 mVelicited a reliable LTD in the subiculum. The LTD did not cause the changes of the paired-pulse ratio of EPSC. Furthermore, it did not depend on either NMDA receptors or voltage-gated calcium channels (VGCCs). Bath application of the G-protein coupled muscarinic acetylcholine receptors (mAChRs) antagonists, atropine or scopolamine, blocked the LTD, suggesting that mAChRs are involved in the LTD. It was also completely blocked by either the Ca2+ chelator BAPTA or the G-protein inhibitor GDP-beta-S in the intracellular solution. This type of LTD in the subiculum may play a particular role in the neural information processing between the hippocampus and neocortex. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Morphine conditioned place preference depends on glucocorticoid receptors in both hippocampus and nucleus accumbens

Learned association between drugs of abuse and context is essential for the formation of drug conditioned place preference (CPP), which is believed to engage many brain regions including hippocampus, and nucleus accumbens (NAc). The underlying mechanisms

NR2B-containing N-methyl-D-aspartate subtype glutamate receptors regulate the acute stress effect on hippocampal long-term potentiation/long-term depression in vivo

Behavioral stress facilitates long-term depression but impairs long-term potentiation in the hippocampus. Recent evidence in vitro demonstrates that the NIR2B-containing N-methyl-D-aspartate subtype glutamate receptor antagonist Ro25-6981 prevents the beh

Opiate withdrawal induces dynamic-expressions of AMPA receptors and its regulatory molecule CaMKII alpha in hippocampal synapses

Adaptive changes in brain areas following drug withdrawal are believed to contribute to drug seeking and relapse. Cocaine withdrawal alters the expression of GluR1 and GluR2/3 subunits of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) rec

Chronic Morphine Treatment Impaired Hippocampal Long-Term Potentiation and Spatial Memory via Accumulation of Extracellular Adenosine Acting on Adenosine A(1) Receptors

Chronic exposure to opiates impairs hippocampal long-term potentiation (LTP) and spatial memory, but the underlying mechanisms remain to be elucidated. Given the well known effects of adenosine, an important neuromodulator, on hippocampal neuronal excitability and synaptic plasticity, we investigated the potential effect of changes in adenosine concentrations on chronic morphine treatment-induced impairment of hippocampal CA1 LTP and spatial memory. We found that chronic treatment in mice with either increasing doses (20-100 mg/kg) of morphine for 7 d or equal daily dose (20 mg/kg) of morphine for 12 d led to a significant increase of hippocampal extracellular adenosine concentrations. Importantly, we found that accumulated adenosine contributed to the inhibition of the hippocampal CA1 LTP and impairment of spatial memory retrieval measured in the Morris water maze. Adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine significantly reversed chronic morphine-induced impairment of hippocampal CA1 LTP and spatial memory. Likewise, adenosine deaminase, which converts adenosine into the inactive metabolite inosine, restored impaired hippocampal CA1 LTP. We further found that adenosine accumulation was attributable to the alteration of adenosine uptake but not adenosine metabolisms. Bidirectional nucleoside transporters (ENT2) appeared to play a key role in the reduction of adenosine uptake. Changes in PKC-alpha/beta activity were correlated with the attenuation of the ENT2 function in the short-term (2 h) but not in the long-term (7 d) period after the termination of morphine treatment. This study reveals a potential mechanism by which chronic exposure to morphine leads to impairment of both hippocampal LTP and spatial memory.