Synapse
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Systemic nicotine‐induced dopamine release in the rat nucleus accumbens is regulated by nicotinic receptors in the ventral tegmental area Abstract Stimulation of the mesolimbic dopamine (DA) system is considered of major importance for the rewarding and dependence producing properties of nicotine (NIC). To identify the site of this stimulatory action, simultaneous microdialysis was performed in the ventral tegmental area (VTA) and the ipsilateral nucleus accumbens (NAC) of awake rats. Extracellular concentrations of DA and its metabolites were measured in the NAC. NIC (0.5 mg/kg, s.c.) increased DA and its metabolites by ∼50%.Concomitant infusion of the nicotinic receptor antagonist mecamylamine (MEC, 100 μ) through the VTA probe, starting 40 min before NIC injection, antagonized the NIC induced increases of DA and its metabolites. In contrast, similar MEC pretreatment (40 or 140 min) in the NAC did not affect DA or metabolite responses to systemic NIC. Infusion of NIC (1,000 μ) in the NAC or the VTA increased DA release by 49% and 48%, respectively, whereas only the VTA infusion increased metabolite concentrations by ‐25%. MEC infusion (1–1,000 μ) in the VTA did not affect DA or its metabolites, whereas the 1,000 μ concentration infused in the NAC increased DA by 77%. These results suggest that nicotinic receptors in the somatodendritic region may be of greater importance than those located in the terminal area for the stimulatory action of systemic NIC on the mesolimbic DA system. Furthermore, our findings support the notion that the mesolimbic dopaminergic system is phasically rather than tonically regulated by nicotinic receptor activation within the VTA. © 1994 Wiley‐Liss, Inc.
Synapse - Tập 16 Số 1 - Trang 36-44 - 1994
Inhibition of neuronal nitric oxide synthase attenuates the development of morphine tolerance in rats Abstract Our previous results have shown the involvement of nitric oxide in acute opioid desensitization of μ‐opioid receptors in vitro. In the present study, we investigated the effect of repeated administration of 7‐nitroindazole (7‐NI; 30 mg/kg/12 h, i.p., 3 days), an inhibitor of neuronal nitric oxide synthase in vivo, on μ‐opioid receptor tolerance induced by subchronic treatment with morphine in rats. The inhibitory effect of the opioid agonist Met5 ‐enkephalin (ME) on the cell firing rate was evaluated by single‐unit extracellular recordings of noradrenergic neurons in the locus coeruleus from brain slices, and the antinociceptive effect of morphine was measured by tail‐flick techniques. In morphine‐treated animals, concentration‐effect curves for ME in the locus coeruleus were shifted by 5‐fold to the right as compared to those in sham‐treated animals, which confirmed the induction of μ‐opioid receptor tolerance. However, tolerance to ME in morphine‐treated rats was fully prevented by co‐administration of 7‐NI when compared to the vehicle‐morphine group. Likewise, the antinociceptive effect of morphine was reduced in morphine‐treated animals as compared to the sham group, whereas the antinociceptive tolerance was partially prevented by co‐administration of 7‐NI in morphine‐treated rats (when compared to the vehicle‐morphine group). Finally, 7‐NI administration in sham‐treated rats failed to change the effect induced by ME on the locus coeruleus or by morphine in the tail‐flick test as compared to vehicle groups. These results demonstrate that subchronic administration of a neuronal inhibitor of nitric oxide synthase attenuates the development of morphine tolerance to the cellular and analgesic effects of μ‐opioid receptor agonists. Synapse 57:38–46, 2005. © 2005 Wiley‐Liss, Inc.
Synapse - Tập 57 Số 1 - Trang 38-46 - 2005
Melatonin protects against amyloid-β-induced impairments of hippocampal LTP and spatial learning in rats
Synapse - Tập 67 Số 9 - Trang 626-636 - 2013
Functional analysis of MOR‐1 splice variants of the mouse mu opioid receptor gene <i>Oprm</i> Abstract A series of mu opioid receptor gene Oprm splice variants have been reported that differ only at their C‐terminus. These variants all contain exons 1, 2, and 3 of the gene, the exons responsible for coding all seven transmembrane domains. Whereas MOR‐1 also has exon 4 that encodes for an additional 12 amino acids at the tip of the C‐terminus, the other MOR‐1 variants have unique amino acid sequences distinct from those in MOR‐1 due to alternative splicing. All these variants are mu‐selective in binding assays. The current study explored the ability of these variants to stimulate [35 S]GTPγS binding to assess them functionally. Only mu opioids stimulated [35 S]GTPγS binding. Among the mu opioids we noted marked differences in their maximal stimulation among the clones. This was most prominent with β‐endorphin, which stimulated [35 S]GTPγS binding in the MOR‐1E expressing cells to a greater degree than [D‐Ala2 ,MePhe4 ,Gly(ol)5 ]enkephalin (DAMGO; 130%) and was far less effective than DAMGO in MOR‐1C cells (44%). The rank order of maximal stimulation of the drugs varied among the clones as well. Dynorphin A, β‐endorphin and morphine were most effective in stimulating [35 S]GTPγS binding in MOR‐1E, while M6G and fentanyl were most effective in MOR‐1 expressing cells. The potency (EC50 ) of some of the drugs also varied extensively among the clones, with a poor correlation between the potency of the drugs to stimulate [35 S]GTPγS binding and their binding affinity. Together, these findings reveal marked functional differences among the variants that only can be explained by their structural differences at the tip of their C‐terminus. Synapse 51:11–18, 2004. © 2003 Wiley‐Liss, Inc.
Synapse - Tập 51 Số 1 - Trang 11-18 - 2004
Effects of birth insult and stress at adulthood on in vivo tyrosine hydroxylase and tryptophan hydroxylase activities in rat brain
Synapse - Tập 47 Số 1 - Trang 87-89 - 2003
Multiple metabotropic glutamate receptors regulate hippocampal function Abstract Selective activation of metabotropic glutamate receptors withtrans ‐1‐amino‐1, 3‐cyclopentanedicarboxylic acid (trans ‐ACPD) stimulates phosphoinositide hydrolysis and elicits three major physiological responses in area CA1 of the hippocampus. These include direct excitation of pyramidal cells, blockade of synaptic inhibition, and decreased transmission at the Schaffer collateral‐CA1 pyramidal cell synapse. Physiological effects oftrans ‐ACPD are thought to be mediated by activation of phosphoinositide hydrolysis. However, it is now clear that multiple metabotropic glutamate receptor subtypes exist, some of which are not coupled to phosphoinositide hydrolysis. Thus, we performed a series of studies aimed at determining whether the physiological effects oftrans ‐ACPD in the hippocampus are mediated by activation of the predominant phosphoinositide hydrolysis‐linked glutamate receptor. We report thatL ‐2‐amino‐3‐phosphonopropionic acid (L ‐AP3), an antagonist oftrans ‐ACPD‐stimulated phosphoinositide hydrolysis, does not inhibit the physiological effects oftrans ‐ACPD in area CA1 at concentrations that maximally inhibittrans ‐ACPD‐stimulated phosphoinositide hydrolysis in this region. Furthermore, 1S, 3S‐ACPD activates the phosphoinositide hydrolysis‐linked glutamate receptor but does not reduce evoked field excitatory postsynaptic potentials (EPSPs) in area CA1. However, we report that the physiological effects of 1R, 3S‐ and 1S, 3R‐ACPD are consistent with the hypothesis that these effects are mediated by activation of a metabotropic glutamate receptor. Thus, our data are consistent with the hypothesis that the physiological effects oftrans ‐ACPD in area CA1 of the hippocampus are mediated by metabotropic glutamate receptors that are distinct from the AP3‐sensitive phosphoinositide hydrolysis‐linked glutamate receptor. © 1992 Wiley‐Liss, Inc.
Synapse - Tập 12 Số 3 - Trang 206-213 - 1992
Elevations of nucleus accumbens dopamine and DOPAC levels during intravenous heroin self‐administration Abstract Extracellular dopamine and DOPAC (3,4‐dihydroxyphenylacetic acid) levels in nucleus accumbens were sampled by microdialysis and quantified with high‐ performance liquid chromatography during intravenous heroin self‐administration sessions in rats. Dopamine levels in 10 and 20 min samples were elevated following the first injection of each session, reaching a plateau of elevation within the first two or three injections and falling back toward baseline only when drug access was terminated. Elevations were in the range of 150–300% when unit dosages of 0.05–0.2 mgkg were given. Increasing the work requirement from FR‐1 to FR‐10 did not appear to alter the degree of elevation of dopamine levels, and dopamine levels fell during extinction while lever‐pressing rates increased 20‐fold. While animals compensated for unit dose changes between 0.05 and 0.2 mg/kg/injection, adjusting their response rate such that the same hourly drug intake and the same asymptotic dopamine levels were maintained across these conditions, at 0.4 mg/kg/injection hourly drug intake and asymptotic dopamine levels were elevated beyond the levels sustained by the lower doses. These findings confirm that self‐administered doses of intravenous heroin are sufficient to activate the mesolimbic dopamine system and suggest that significant heroin “craving” can emerge when dopamine levels are still moderately elevated, long before the development of dopamine depletion associated with opiate withdrawal. © 1995 Wiley‐Liss, Inc.
Synapse - Tập 21 Số 2 - Trang 140-148 - 1995
Defective hippocampal mossy fiber long‐term potentiation in endothelial nitric oxide synthase knockout mice Abstract Mossy fiber long‐term potentiation (mfLTP) was compared in hippocampal slices prepared from wild‐type mice and mice lacking functional endothelial nitric oxide synthase (eNOS‐/‐ mice) using field potential recording. In the presence of D‐2‐amino‐5‐phosphonovaleric acid (AP5, 50 μM), the mfLTP induced by tetanic stimulation (100 Hz, 1 sec) was significantly reduced in knockouts (n = 8) in comparison with wild‐type (n = 8). Similarly, potentiation induced by forskolin (30 μM) or 8‐bromo‐cyclic adenosine monophosphate (8‐Br‐cAMP, 100 μM) was less pronounced in knockouts. However, in wild‐types the mfLTP‐induced in the presence of the nonselective pharmacological inhibitor of NOS (N‐nitro‐L‐Arginine, 100 μM, n = 6) was not significantly different from control (n = 8). Thus, eNOS is not directly involved in mfLTP, but lack of eNOS during development leads to a deficit downstream of adenylyl cyclase. Synapse 41:191–194, 2001. © 2001 Wiley‐Liss, Inc.
Synapse - Tập 41 Số 3 - Trang 191-194 - 2001
PET imaging of glucose metabolism in a mouse model of temporal lobe epilepsy
Synapse - Tập 59 Số 2 - Trang 119-121 - 2006
Quantitation of Carbon‐11‐labeled raclopride in rat striatum using positron emission tomography Abstract Using conventional autoradiographic and tissue counting techniques, the experimental quantitation of in vivo kinetics of prospective or established radioligands for PET is animal and labour intensive. The present study tested the feasibility of using PET itself to quantitate the specific binding of [11 C] raclopride to rat striatum and to study the effects of experimental manipulation of endogenous dopamine on binding parameters. Carbon‐11‐labeled raclopride was given i. v. to anaesthetised rats, positioned in a PET camera and dynamic emission scans acquired over 60 min. Time‐activity curves were generated for selected regions of interest, representing striatum and cerebellum and the striatal data fitted to a compartmental model, using cerebellum as the input function, thus circumventing the need for individual metabolite‐corrected plasma curves. In control rats, the binding potential (BP), defined as the ratio of the rate constants for transfer from “free to bound” and “bound to free” compartments, was of the order of 0.6. This was reduced threefold by predosing with nonraioactive raclopride. Increasing extracellular dopamine levels by predosing with d ‐amphetamine resulted in a significant decrease in BP whereas reducing extracellular dopamine by predosing with γ‐butyrolactone caused a significant increase. Thus, despite the limitation in spatial resolution of PET, specific binding of raclopride could be assessed from regional time‐activity curves from individual rats. The system was sufficiently sensitive that changes in BP could be detected following modulation of endogenous dopamine levels, a finding of potential relevance to the interpretation of clinical PET data.
Synapse - Tập 12 Số 1 - Trang 47-54 - 1992
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