scholarly journals The Role of NMDA receptors in rat propofol self-administration

2020 ◽  
Author(s):  
Bei ping Chen ◽  
Xi-xi Huang ◽  
Dong-mei Dong ◽  
Hui Wu ◽  
Tian-qi Zhu ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Neural Plasticity ◽  
Fixed Ratio ◽  
Study Groups ◽  
Ratio Schedule ◽  
Self Administration ◽  
Mk 801 ◽  
Anesthetic Agents ◽  
Administration Methods

Abstract Aim Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators of both neural plasticity and development, as well as of addiction and neurodegeneration. Herein we explored the role of these receptors in rat propofol self-administration. Methods Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using an FR fixed ratio schedule of the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, and then 10 minutes later were subjected to a propofol self-administration session. Results: After training, rats had acquired the ability to self-administer propofol successfully, as evidenced by a significant and stable rise in active nose-pokes leading to propofol administration relative to control nose-pokes (P<0.01) and became stable. Relative to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited significantly more propofol infusions (F(3, 28)=4.372, P<0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg. In addition, MK-801 failed to alter numbers of active (F(3, 28)=1.353, P>0.05) or inactive (F(3, 28)=0.047, P>0.05) responses in study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg (P=0.006, P<0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group exhibited a significant reduction in the number of active nose poke responses (F(3, 20)=20.8673, P<0.01) and the number of sucrose pellets (F(3, 20)=23.77, P<0.01), with increased locomotor activity (F(3, 20)=22.812, P<0.01). Conclusion These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.

scholarly journals The Role of NMDA receptors in rat propofol self-administration

2020 ◽  
Author(s):  
Bei ping Chen ◽  
Xi-xi Huang ◽  
Dong-mei Dong ◽  
Hui Wu ◽  
Tian-qi Zhu ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Neural Plasticity ◽  
Fixed Ratio ◽  
Study Groups ◽  
Ratio Schedule ◽  
Self Administration ◽  
Mk 801 ◽  
Anesthetic Agents ◽  
Administration Methods

Abstract Aim Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators of both neural plasticity and development, as well as of addiction and neurodegeneration. Herein we explored the role of these receptors in rat propofol self-administration. Methods Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using an FR fixed ratio schedule of the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, and then 10 minutes later were subjected to a propofol self-administration session. Results: After training, rats had acquired the ability to self-administer propofol successfully, as evidenced by a significant and stable rise in active nose-pokes leading to propofol administration relative to control nose-pokes (P<0.01) and became stable. Relative to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited significantly more propofol infusions (F(3, 28)=4.372, P<0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg. In addition, MK-801 failed to alter numbers of active (F(3, 28)=1.353, P>0.05) or inactive (F(3, 28)=0.047, P>0.05) responses in study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg (P=0.006, P<0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group exhibited a significant reduction in the number of active nose poke responses (F(3, 20)=20.8673, P<0.01) and the number of sucrose pellets (F(3, 20)=23.77, P<0.01), with increased locomotor activity (F(3, 20)=22.812, P<0.01). Conclusion These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.

scholarly journals The Role of NMDA receptors in rat propofol self-administration

2020 ◽  
Author(s):  
Bei ping Chen ◽  
Xi-xi Huang ◽  
Dong-mei Dong ◽  
Hui Wu ◽  
Tian-qi Zhu ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Neural Plasticity ◽  
Fixed Ratio ◽  
Study Groups ◽  
Ratio Schedule ◽  
Self Administration ◽  
Mk 801 ◽  
Anesthetic Agents ◽  
Administration Methods

Abstract Aim Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators of both neural plasticity and development, as well as of addiction and neurodegeneration. Herein we explored the role of these receptors in rat propofol self-administration. Methods Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using an FR fixed ratio schedule of the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, and then 10 minutes later were subjected to a propofol self-administration session. Results: After training, rats had acquired the ability to self-administer propofol successfully, as evidenced by a significant and stable rise in active nose-pokes leading to propofol administration relative to control nose-pokes (P<0.01) and became stable. Relative to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited significantly more propofol infusions (F(3, 28)=4.372, P<0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg. In addition, MK-801 failed to alter numbers of active (F(3, 28)=1.353, P>0.05) or inactive (F(3, 28)=0.047, P>0.05) responses in study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg (P=0.006, P<0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group exhibited a significant reduction in the number of active nose poke responses (F(3, 20)=20.8673, P<0.01) and the number of sucrose pellets (F(3, 20)=23.77, P<0.01), with increased locomotor activity (F(3, 20)=22.812, P<0.01). Conclusion These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.

scholarly journals The Role of NMDA receptors in rat propofol self-administration

2020 ◽  
Author(s):  
Bei ping Chen ◽  
Xi-xi Huang ◽  
Dong-mei Dong ◽  
Hui Wu ◽  
Tian-qi Zhu ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Neural Plasticity ◽  
Neuronal Development ◽  
Fixed Ratio ◽  
Study Groups ◽  
Sprague Dawley ◽  
Self Administration ◽  
Mk 801 ◽  
Anesthetic Agents

Abstract Background: Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators neural plasticity, neuronal development, addiction, and neurodegeneration. In the present study, we explored the role of these receptors in the context of rat propofol self-administration. Methods: Sprague-Dawley Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using a fixed-ratio (FR) schedule over the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, followed 10 minutes later by a propofol self-administration session. Results: After training, rats successfully underwent acquisition of propofol self-administration, as evidenced by a significant and stable rise in the number of active nose-pokes resulting in propofol administration relative to the number of control inactive nose-pokes (P<0.01). As compared to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited a significantly greater number of propofol infusions (F (3, 28) = 4.372, P<0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg of this compound. In addition, MK-801 failed to alter the numbers of active (F (3, 28) = 1.353, P>0.05) or inactive (F (3, 28) = 0.047, P>0.05) responses in these study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg MK-801 (P=0.006, P<0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group displayed a significant reduction in the number of active nose-poke responses (F(3, 20)=20.8673, P<0.01) and the number of sucrose pellets (F(3, 20)=23.77, P<0.01), while their locomotor activity was increased (F(3, 20)=22.812, P<0.01). Conclusion: These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.

Role of N-methyl-D-aspartate receptors in the pontine pneumotaxic mechanism in the cat

1994 ◽  
Vol 76 (3) ◽  
pp. 1138-1143 ◽  
Author(s):  
L. Ling ◽  
D. R. Karius ◽  
D. F. Speck
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Partial Recovery ◽  
Inspiratory Time ◽  
Systemic Injection ◽  
Lung Inflation ◽  
Mk 801 ◽  
Efferent Limb ◽  
Adult Cats

Systemic injection of MK-801, an N-methyl-D-aspartate (NMDA) receptor-associated channel blocker, induces an apneusis in vagotomized cats similar to that produced by pontine respiratory group (PRG) lesions, suggesting the possible involvement of NMDA receptors in the pontine pneumotaxic mechanism. Previous results from our laboratory indicate that the efferent limb of the pontine pneumotaxic mechanism is unlikely to require NMDA receptor-mediated neurotransmission. Therefore, the present study examined the potential involvement of PRG NMDA receptors in the pontine pneumotaxic mechanism. Experiments were conducted in decerebrate, paralyzed, and ventilated adult cats. The effects on inspiratory time (TI) of MK-801 microinjection into PRG were tested in 12 cats. Pressure microinjection of MK-801 (15 mM, 80–3,000 nl) significantly prolonged TI in all animals when lung inflation was withheld. TI progressively increased in most animals for > or = 30 min. After this period, partial recovery of the effect occurred in eight cats as TI shortened toward predrug levels. In three animals, microinjection of MK-801 induced a complete apneusis in the absence of lung inflation from which there was no detectable recovery. Microinjections into regions approximately 2 mm distant from PRG produced little or no effect. These results provide evidence that NMDA receptors located in the region of PRG play an important functional role in the control of the breathing cycle.

scholarly journals Cocaine self-administration by rats is inhibited by cyclic GMP-elevating agents: involvement of epigenetic markers

2013 ◽  
Vol 16 (7) ◽  
pp. 1587-1597 ◽  
Author(s):  
Elodie Deschatrettes ◽  
Pascal Romieu ◽  
Jean Zwiller
Keyword(s):  
Prefrontal Cortex ◽  
Cyclic Gmp ◽  
Present Report ◽  
Fixed Ratio ◽  
Signal Transduction Pathway ◽  
Adult Brain ◽  
Ratio Schedule ◽  
Self Administration ◽  
Epigenetic Markers ◽  
Histone Deacetylase 2

Abstract The C-type natriuretic peptide (CNP) exerts its action via stimulation of the cyclic GMP (cGMP) signalling pathway, which includes the activation of cGMP-dependent protein kinases. The pathway can also be activated by inhibitors of phosphodiesterases (PDE) that hydrolyse cGMP. The present report shows that activation of the cGMP pathway by CNP, by bromo-cGMP, a cell-permeant cGMP analogue, or by the PDE inhibitor zaprinast dose dependently reduces intravenous cocaine self-administration by rats. The effect was found when the compounds were injected in situ into the prefrontal cortex, but not when they were injected into the nucleus accumbens. A decrease in the number of cocaine infusions performed by rats was obtained under the fixed ratio-1 schedule of reinforcement as well as under a progressive ratio schedule, which evaluates the motivation of the animals for the drug. Decrease in cocaine self-administration was accompanied with reduced expression of the epigenetic markers methyl-CpG-binding protein 2 (MeCP2) and histone deacetylase 2 (HDAC2) in dopaminergic projection areas. An increase in the acetylation level of histone H3, but not of histone H4, was also noticed. Since MeCP2 and HDAC2 are known to modulate dynamic functions in the adult brain, such as synaptic plasticity, our results showing that activation of the cGMP signal transduction pathway decreased both cocaine intake and expression of the epigenetic markers strongly suggest that the MeCP2/HDAC2 complex is involved in the analysis of the reinforcing properties of cocaine in the prefrontal cortex.

The N-methyl-d-aspartate receptor antagonist MK-801 delays the onset of puberty and may acutely block the first spontaneous LH surge and ovulation in the rat

1991 ◽  
Vol 131 (3) ◽  
pp. 435-441 ◽  
Author(s):  
H. M. A. Meijs-Roelofs ◽  
P. Kramer ◽  
E. C. M. van Leeuwen
Keyword(s):  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Acute Treatment ◽  
Physiological Role ◽  
Female Rat ◽  
Mk 801 ◽  
Aspartate Receptor ◽  
Serum Lh ◽  
Lh Secretion

ABSTRACT The physiological role of activated hypothalamic N-methyl-d-aspartate (NMDA) receptors during the final phase of female sexual maturation was explored in the rat. The effects of administration of the specific non-competitive receptor antagonist MK-801 on the occurrence of first ovulation and on LH secretion were studied. Injections of MK-801 (0·1–0·2 mg/kg body wt, s.c.) were given once or twice daily, starting at 28 or 35 days of age and continuing up to the day of first ovulation, resulted in a significant delay of this ovulation. Rats that were treated daily with 0·2 mg MK-801/kg, starting on days 30 or 34 and continuing up to day 38, but not including the day of first pro-oestrus, also showed retarded first ovulation. No decrease in serum LH concentration, compared with control rats, could be detected in these rats. Acute treatment with MK-801 (one or two injections of 0·2, or one injection of 0·5 mg/kg) given at 11.30 h (and 16.00 h) on the day of first pro-oestrus produced partial (1 × 0·2 mg/kg) or complete (2×0·2 and 1 × 0·5 mg/kg) blockade of first ovulation; blocked rats ovulated 1 day later. Serum LH concentrations at 16.00 h on the day of pro-oestrus were significantly decreased in all MK-801-treated groups compared with saline-injected control rats. At 19.00 and 22.00 h LH concentrations remained low in all non-ovulating MK-801-treated rats, but increased in the MK-801-treated rats that ovulated. Thus chronic blockade of the NMDA receptors by the antagonist MK-801 delays but does not prevent first ovulation, whereas acute treatment blocks the pro-oestrous LH peak. It was concluded that activation of NMDA receptors plays an important role both in tonic and preovulatory LH secretion during the onset of puberty in the female rat. Journal of Endocrinology (1991) 131, 435–441

scholarly journals Short Therapeutic Window for MK-801 in Transient Focal Cerebral Ischemia in Normotensive Rats

1996 ◽  
Vol 16 (1) ◽  
pp. 107-113 ◽  
Author(s):  
I. Margaill ◽  
S. Parmentier ◽  
J. Callebert ◽  
M. Allix ◽  
R. G. Boulu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Nmda Receptors ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Activity ◽  
Therapeutic Window ◽  
Left Middle Cerebral Artery ◽  
Mk 801 ◽  
Transient Focal Cerebral Ischemia

The present study investigates the role of N-methyl-D-aspartate (NMDA) receptors in a model of transient focal cerebral ischemia in normotensive rats. The left middle cerebral artery and both common carotid arteries were occluded for 60 min. Preliminary studies indicated that this gave reproducible infarctions of the cortex and striatum. These infarctions were the result of severe ischemia followed by complete reperfusion after clamp removal, as showed by striatal tissue Po2 monitoring. Microdialysis indicated that glutamate concentration increased immediately after occlusion and returned to the baseline value 40 min after clamp removal. MK-801 (1 mg kg−1 i.v.), an antagonist of the NMDA glutamatergic receptor, reduced the cortical infarct volume by 29% (p < 0.001) and the striatal infarct volume by 14% (p < 0.05) when given just prior to ischemia, but had no neuroprotective activity when given 30 min after the onset of ischemia. This short therapeutic window for MK-801 suggests that NMDA receptors play only a transient role in reversible focal ischemia in rats.

scholarly journals Dramatic increase in lever-pressing activity in rats after training on the progressive ratio schedule of cocaine self-administration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vladimir L. Tsibulsky ◽  
Andrew B. Norman
Keyword(s):  
Fixed Ratio ◽  
Progressive Ratio ◽  
Ratio Schedule ◽  
Self Administration ◽  
The Press ◽  
Second Mode ◽  
Before And After ◽  
Lever Pressing ◽  
Remission Phase ◽  
Definition Of

AbstractTransition from the highest rate of lever-pressing activity during the unloading (extinction) phase of a cocaine self-administration session to an extremely low activity rate during the remission phase is in many cases gradual. This makes it difficult to assess the duration of the unloading phase after a fixed ratio 1 (FR1) or breakpoint after a progressive-ratio (PR) self-administration session. In addition, 3–5 days of training under the PR schedule results in a dramatic and persistent increase in the rate of presses during PR sessions and in the unloading phase following FR1 self-administration sessions. The goals of this study were to find the definition of the last press demarcating the border between the unloading and remission phases of the session and to determine if this border was also affected by PR training. Rats were trained to self-administer cocaine under the FR1 schedule and then under the PR schedule of drug delivery. Distributions of inter-press intervals (IPIs) during the unloading phase in sessions before and after PR training were compared. It was found that the distribution of cocaine-induced IPIs during the unloading phase was lognormal, bimodal, and independent of previously injected cocaine unit doses. The first mode represented intervals within the short bouts of stereotypic presses and the second mode represented intervals between bouts. The two modes were approximately 0.7 s and 21 s during unloading prior to and 0.6 s and 1.5 s after PR self-administration training. The total number of presses per unloading phase increased eightfold. When the FR1 schedule was restored, the intervals between bouts remained very short for at least 7–10 days and only then started a gradual increase towards baseline levels. The last unloading press was defined as the press followed by the IPI longer than the defined criterion. PR training resulted in a substantial and long-lasting increase in lever-pressing activity during unloading. The duration of the unloading phase did not depend on the rate of lever-pressing activity.

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