摘要:

CHRONIC intermittent exposure to psychomotor stimulants induces in the striatum the expression of Fos- related proteins (Fras) that persist after the end of drug treatment. We carried out experiments to determine whether such Fras (‘chronic Fras’) require dopamine D1-class receptor function for their persistent expression in the striatum. We chronically administered cocaine to rats in a behavioral sensitization protocol and blocked D1- class receptors with SCH23390 before a final cocaine challenge. Western blotting and immunohistochemical analyses indicate that Fras persistently expressed in response to chronic treatment include proteins of two types: those that have become independent of D1-class dopamine receptor activation and those that remain dependent on D1-class receptors for their expression following drug challenge.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

COADMINISTRATION of phentermine and fenfluramine has been used to treat cocaine dependence. Patients who relapse while receiving this treatment report diminished subjective effects of cocaine. Due to the importance of mesolimbic dopamine (DA) in mediating cocaine reinforcement, we hypothesized that phentermine might attenuate the effects of cocaine on DA transmission. We examined this proposal directly usingin vivomicrodialysis methods in the nucleus accumbens of awake rats. Rats were pretreated with saline or phentermine (1 mg kg−1, i.v.) and then challenged with cocaine (3 mg kg−1,i.v.). Phentermine alone caused a modest increase in DA, and phentermine pretreatment substantially reduced the cocaine-induced rise in extracellular DA. Phentermine did not alter the stimulatory effect of cocaine on 5-HT. Our findings suggest that phentermine may antagonize the subjective effects of cocaine in humans via a DA mechanism.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

NTERLEUKIN-2 (IL-2) was found to have an analgesic effect in the peripheral nervous system. Both electro- physiological and behavioural experiments suggested an anti-noceiceptive effect of IL-2 in animals. Biochemical experiments revealed that IL-2 could displace diprenorphine binding in both NG 108-15 cells and HEK 293 cells transfected with pCDNA3-DOR (δ opioid receptor). Furthermore, IL-2 significantly inhibited cAMP production stimulated by forskolin in both NG 108-15 and transfected HEK 293 cells, indicating that the binding of IL-2 to the δ opioid receptor is functional.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

7-CHLOROKYNURENIC acid (7-Cl-KYNA) and 5,7-dichlorokynurenic acid (5,7-Cl2-KYNA) are of therapeutic interest as potent glycine/N-methyl-D-aspartate (NMDA) receptor antagonists, but are excluded from brain by the blood–brain barrier. We examined whether these compounds could be delivered to brain through their respective precursors,L-4-chlorokynurenine(4-Cl- KYN) and L-4,6-dichlorokynurenine (4,6-Cl2-KYN), which are amino acids. 4-Cl-KYN was shown to be rapidly shuttled into the brain by the large neutral amino acid transporter of the blood–brain barrier (Km= 105 ± 14 μM, Vmax= 16.9 ± 2.3 nmol min−1g−1) and to be converted intracerebrally to 7-Cl-KYNA. 4,6-Cl2-KYN also expressed affinity for the transporter, but four-fold less than that of 4-Cl-KYN. In summary, the results show that because of their facilitated uptake 4-Cl-KYN and 4,6-Cl2-KYN might be useful prodrugs for brain delivery of glycine-NMDA receptor antagonists.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

FUNCTIONAL areas were detected with short stimuli eliciting transient brain activity using the method of ‘transient’ regions of interest (ROIs) and functional magnetic resonance imaging (fMRI). This method was validated by comparing the results with sustainedly activated areas identified conventionally. Eighty-eight and 89% of the total areas of transient ROIs derived from 0.2 and 2 s stimulation, respectively, were identified at 5–7 s and 5–9 s, respectively, after stimulus onset. Eighty-eight and 76%, respectively, of these areas overlapped ‘conventional’ ROIs derived from 20 s stimulation. These results suggest that the delineation of transient ROIs, by targeting a period ∼7 s after transient neural activity, can be useful for fMRI studies of cognitive functions.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

IN situhybridization for TrkA mRNA was combined with quantitative optical densitometry to evaluate whether the expression of this gene is altered within cholinergic basal forebrain neurons (CBF) in Alzheimer's disease (AD). TrkA mRNA within individual nucleus basalis neurons was significantly reduced (66%) in AD cases relative to aged controls. Reverse transcription polymerase chain reaction quantitative analyses confirmed that TrkA mRNA levels decreased markedly in AD. In contrast, expression of the gene coding for for the low affinity p75NTRwas not significantly altered in AD relative to aged controls. These data indicate that there is a selective defect intrkAgene expression in AD, supporting the hypothesis that the degeneration of CBF neurons seen in this disease results from impaired nerve growth factor trophic support.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

DOPAMINE (DA) is released in the medial preoptic area (MPOA) of male rats during copulation. DA agonists infused into the MPOA facilitate, and antagonists impair, copulatory behavior. Local administration of the nitric oxide (NO) precursor L-arginine also increases DA release in the MPOA. The present experiment used microdialysis to test whether NO promotes DA release during copulation. Males received either an NO synthesis inhibitor, nitro-L-arginine methyl ester (L-NAME, 400μM), or its inactive isomer D-NAME (400μM) into the MPOA via a microdialysis probe for 3 h prior to the introduction of a female. Following D-NAME administration, DA increased during copulation, while L-NAME prevented this increase. NO may therefore promote DA release in the MPOA of male rats, thereby facilitating copulation.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

MULTIPLE forms of synaptic potentiation have been described, but their invovement in development versus learning is unknown. To address this, we examined whether long-term potentiation (LTP) in visual cortex requires protein or RNA synthesis using slice preparations. Theta-burst stimulation of white matter induced two distinct types of LTP in layer 4. A slowly developing LTP, preferentially induced in juveniles, was blocked by protein and RNA synthesis inhibitors and was L-type calcium channel dependent. A quickly developing LTP, induced in juveniles and adults, was independent of macromolecular synthesis and requiredN-methyl-D-aspartate receptor activation. Thus, slow LTP might account for developmental plasticity in visual cortex including the activity-dependent refinement of neural circuitry while fast LTP might underlie the changes in synaptic strength that may participate in visual learning and memory.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

THE effects of acute lowering of body temperature on afferent sensory transmission to the primary somatosensory cortex were determined quantitatively in anaesthetized rats and hamsters. Rats showed no change in afferent sensory transmission until 27°C, but dramatic suppression between 26°C and 22°C, reaching 100% inhibition at 21°C. Hamsters exhibited gradual suppression of sensory transmission from 34°C to 18°C, reaching 95% inhibition at 18°C. Differential effects were also observed during rewarming up to 37°C. Response latencies were also differentially affected during hypothermia in rats and hamsters. These results suggest the presence of inherently different neural mechanisms to process somatosensory information during transient lowering of body temperature between hibernators and nonhibernators.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

APPROXIMATELY 30% of patients with fatal head injuries have deposits of amyloid β-protein (Aβ); these are predominantly individuals carrying the ε4 allele of apolipoprotein E (apoE). Aβ deposition occurs in Alzheimer's disease (AD), for which approximately 50% of the genetic risk is attributed to apoEe 4. The 1,1 geno- type of a presenilin-1 (PS-1) polymorphism has been suggested to account for about half of the remaining genetic risk for AD. We related the PS-1 genotypes of 90 head-injured individuals to Aβ deposition and apoE genotype. There was no difference in PS-1 genotype or allele frequencies between individuals with and without Aβ deposits. Eighteen of 23 individuals with Aβ deposits had apoE ε4 as a risk factor. Three of five individuals without apoE ε4 had the PS-1 1,1 genotype. If PS-1 geno- type influences Aβ deposition the effect is small and is overwhelmed by that of apoE genotype.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID