Acetylcholine Release In Rat Hippocampus Research Articles

Effects of volatile anesthetics on the circadian rhythms of rat hippocampal acetylcholine release and locomotor activity

General anesthesia is occasionally associated with postoperative complications such as sleep disorder, drowsiness, or mood alterations. Hippocampal acetylcholine (ACh), the extracellular level of which increases during the dark (active) phase and decreases during the light (rest) phase in rats, is thought to be associated with locomotor activity and be crucial for learning and memory. Propofol, an intravenous anesthetic, is known to shift the circadian rhythms of physiological parameters including locomotor activity and body temperature in both rodents and humans, while the effects of volatile anesthetics on the circadian rhythm largely remain unclear. The present study examined the effects of isoflurane anesthesia on the diurnal changes in hippocampal ACh release and locomotor activity in rats. Rats were divided into three groups: a light-phase anesthesia group (LA group), a dark-phase anesthesia group (DA group), and a control group. They were exposed to a 12-h light/12-h dark environment and anesthetized with 1.4% isoflurane for 4h during the middle of the light phase (LA group) and dark phase (DA group). Simultaneous measurement of hippocampal ACh by microdialysis and locomotor activity were done for 60h under free-moving conditions. Hippocampal ACh release and locomotor activity showed a clear circadian rhythm. In the DA group, but not in the LA group, the diurnal variation in ACh release was significantly disturbed and a more than 2-h phase-advance in locomotor activity was observed. There was a significant correlation between hippocampal ACh release and locomotor activity, and isoflurane anesthesia disrupted it even after anesthesia was discontinued. This study revealed that the levels and circadian rhythms of hippocampal ACh release and locomotor activity were more sensitive to isoflurane anesthesia when it was administered during the active phase. Our findings suggest that anesthesia exerts differential effects on the regulation of circadian rhythms depending on the circadian phase.

Chronic ethanol consumption does not affect action of propofol on rat hippocampal acetylcholine release in vivo

The aim of this study was to examine ethanol-consumption-related changes in the effects of propofol on rat hippocampal acetylcholine (ACh) release. Male Sprague-Dawley rats received a solution of ethanol (20% v/v) for 24 weeks while controls received tap water. The effects of propofol were examined by in vivo microdialysis, with ACh release from the hippocampal regions determined by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). Propofol 50 mg kg(-1) i.p. significantly decreased basal hippocampal ACh release in ethanol-treated and control rats by 50.4 (sem 4.7)% and 38.3 (11.1)%, respectively. Propofol 100 mg kg(-1) i.p. significantly decreased basal hippocampal ACh release in ethanol-treated and control rats by 67.5 (3.7)% and 55.9 (7.4)%, respectively. The reduction in hippocampal ACh release induced by 50 or 100 mg kg(-1) i.p. propofol was not significantly different between ethanol-treated and control rats. There was no significant difference in the duration of sleep between the two groups. These results demonstrate that chronic ethanol consumption does not augment the inhibitory actions of propofol on rat hippocampal ACh release. These findings appear to be inconsistent with the notion that chronic ethanol intake enhances the propofol-induced inhibition of the hippocampal cholinergic system and related mental dysfunction.

Opposite effects of depressant and convulsant barbiturate stereoisomers on acetylcholine release from the rat hippocampus in vivo

It has been shown that the R(-) isomer of 1-methyl-5-phenyl-5-propyl barbituric acid (MPPB) induces loss of the righting reflex (LRR), while S(+)-MPPB causes pure excitatory effects, including convulsions, in vivo. We studied the effects of the depressant and convulsant MPPB stereoisomers on rat hippocampal acetylcholine (ACh) release in vivo, using a brain microdialysis technique in freely moving animals. R(-)-MPPB 60 and 90 mg x kg(-1) i.p. decreased ACh release from the rat hippocampus by 44.1 (8.2)% and 60.8 (8.2)%, respectively. In the hippocampus, the local application of bicuculline, a gamma-aminobutyric acid (GABA)(A) receptor antagonist, 1 micromol litre(-1) antagonized the inhibitory effects of R(-)-MPPB 90 mg x kg(-1) i.p. In contrast, R(-)-MPPB, S(+)-MPPB 60 and 90 mg x kg(-1) i.p. increased ACh release to 151.8 (6.8)% and 169.6 (11.1)% of the basal release, respectively. Our results demonstrated that R(-)-MPPB decreased, while S(+)-MPPB increased, rat hippocampal ACh release and that the inhibitory effects of R(-)-MPPB may involve the GABA(A) receptor in vivo. These data imply that changes in hippocampal ACh due to these agents may be related to their central inhibitory and stimulatory actions in vivo.

Age‐related modifications of effects of ketamine and propofol on rat hippocampal acetylcholine release studied by in vivo brain microdialysis

We sometimes encounter impairment of learning and memory after general anesthesia in elderly patients. The aim of this study was to examine age-related modifications of the effects of ketamine and propofol on rat hippocampal acetylcholine (ACh) release because hippocampal cholinergic neurons are supposed to be involved in learning and memory. The experiments were performed on male Wistar young rats (2 months old) and old rats (18 months old), using in vivo brain microdialysis technique under freely moving condition. After initial sampling of three collections, test drugs were administered. The ACh release was determined by the HPLC-ECD method. In old rats, the hippocampal basal ACh release was significantly lower than in young rats. Ketamine (25 and 50 mg kg(-1) i.p.) increased and propofol (25 and 50 mg kg(-1) i.p.) decreased the hippocampal ACh release in both young and old rats. Furthermore, ketamine 50 mg kg(-1) i.p. (anesthetic dose) produced facilitatory effects on the hippocampal ACh release in young rats (193% of the basal release), while in old rats the same dose of ketamine i.p. produced more pronounced facilitatory effects on the hippocampal ACh release (317% of the basal release). On the other hand, propofol 50 mg kg(-1) i.p. (anesthetic dose) produced inhibitory effects on the hippocampal ACh release in young rats (56% of control) and in old rats (77% of control). Although the maximal inhibitory peak effects of propofol 50 mg kg(-1) i.p. did not differ significantly between young rats and old rats, decrease of the hippocampal ACh release in old rats persisted longer than in young rats. Ketamine produced more pronounced facilitatory effects on the hippocampal ACh release in old rats, as compared with young rats. On the other hand, propofol has inhibitory effects on the hippocampal ACh release in young and old rats. The aging process may suppress the ability to recover from the inhibitory anesthetic state induced by propofol.

P-353 - The functional analysis of the muscarinic m2 vs. m4 receptors regulating the rat hippocampal acetylcholine release by antisense oligonucleotides

P-353 - The functional analysis of the muscarinic m2 vs. m4 receptors regulating the rat hippocampal acetylcholine release by antisense oligonucleotides

O-261 - The effect of repeated administration of lithium on rat hippocampal acetylcholine release via serotonin1A receptor

O-261 - The effect of repeated administration of lithium on rat hippocampal acetylcholine release via serotonin1A receptor

Differential contribution of L- and N-type calcium channels on rat hippocampal acetylcholine release

Bay K 8644, nimodipine and ω-conotoxin GVIA (ω-CgTx) were used to study the different contribution of voltage-sensitive calcium channels (VSCC) to [ 3H]acetylcholine ([[ 3ACh) release in rat hippocampal synaptosomes. In our experimental conditions, the percentage of calcium-dependent ACh release was ~80%. Nimodipine (0.01–10 μM) and Bay K 8644 (0.01–10 μM) were not able to modify the [ 3H]ACh release under stimulating conditions (15 mM K +). Nevertheless, when K + concentration was reduced to 8 mM, a significant increase in [ 3H]ACh release was observed at 1 and 10 μM of Bay K 8644. Nimodipine (0.01–10 μM) failed to reverse the effect of Bay K 8644 on [ 3H]ACh release. Finally, ω-CgTx (0.001–1 μM) caused a concentration-dependent reduction of [ 3H]ACh release in K + (15 mM)-stimulating conditions. These results suggest that the N-type VSCC probably play a predominant role in regulating the [ 3H]ACh release in synaptosomes from rat hippocampus.

The benzodiazepine receptor antagonist flumazenil increases acetylcholine release in rat hippocampus

The benzodiazeoine receptor antagonist flumazenil (2.5–20 mg/kg i.p.) increased acetylcholine (ACh) release by up to 85% in the hippocampus of freely moving rats. In contrast, the benzodiazepine receptor full agonist diazepam (2.5–10 mg/kg i.p.) decreased ACh release up to a maximum of 45% in the same brain area. Injection of flumazenil (10 pmol) or diazepam (10 pmol) into the medial septum increased (95%) or reduced (50%), respectively, ACh release in the hippocampus. The maximum effect produced by those drugs was of the same magnitude as that observed after systemic injection. The changes in hippocampal cho cholinergic function elicitec by activation and blockade of benzodiazepine receptors in the medial septum may thus play a crucial role in the alterations of the cognitive processes elicited by benzodiazepine receptor ligands.

Modulation of acetylcholine release in rat hippocampus by amino alcohols and Bay K 8644

The amino alcohols ethanolamine,R-alaninol andR-prolinol were shown to enhance high potassium evoked release of [ 3H]acetylcholine from hippocampal slices by monitoring fractional release of tritium during superfusion. This action appeared to be unique to hippocampal cholinergic nerve terminals becauseR-prolinol did not modulate evoked release acetylcholine from cortical or striatal slices, dopamine from striatal slices or norepinephrine from hippocampal slices. Bay K 8644, a dihydropyridine activator of calcium L-channels, exhibited a similar specificity profile. Bay K 8644 decreased the EC 50 ofR-prolinol without changing the maximal response, indicating that the actions of these two compounds converge through a common cellular mechanism. The effect ofR-prolinol was blocked by the L-channel antagonists diltiazem and verapamil but not by nifedipine. In contrast, nifedipine only and not diltiazem or verapamil, blocked the enhancement induced by Bay K 8644. It appears then that amino alcohols can modulate the release of acetylcholine in the hippocampus possibly by enhancing calcium entry into nerve terminals through a specific activation of presynaptic L-channels at a site other than that which interacts with dihydropyridines.

Monoamine-mediated enhancement of acetylcholine release in rat hippocampus by 6 R- l-erythro-5, 6, 7, 8-tetrahydrobiopterin

Recently, we reported that intracerebroventricular administration of 6 R- l-erythro-tetrahydrobiopterin (6R-BH 4), a common natural cofactor for phenylalanine, tyrosine and tryptophan hydroxylases, enhances in vivo exocytotic release of acetylcholine (ACh) from the rat hippocampus, as monitored by brain microdialysis. In the present study, we developed a method for separation of ACh from 6R-BH 4 on small columns of Sephadex G-10, which allowed us to determine by high pressure liquid chromatography (HPLC) the changes of ACh levels recovered in dialysates following addition of 6R-BH 4 to the dialyzing fluid. Infusions of 6R-BH 4 (final concentration, 0.25, 0.5 and 1 mM in the perfusing fluid) produced concentration-dependent increases in ACh levels in dialysates (1.5-, 3- and 8-fold of the basal levels, respectively), but was without effect on choline levels in dialysates. Infusion of 6 S- l-erythro-5, 6, 7, 8-tetrahydrobiopterin (6S-BH 4), an unnatural diastereoisomer of 6R-BH 4, or l-erythro-biopterin (biopterin), an oxidized form of 6R-BH 4, did not affect the ACh levels in dialysates. The 6R-BH 4-induced increase in ACh levels persisted after pretreatment with atropine, a muscarinic antagonist, but did not occur in rats pretreated with reserpine to deplete monoamines. These results show that 6R-BH 4 stimulates exocytotic ACh release in the hippocampus through action on a local monoaminergic system in the hippocampus.

Arginine-vasopressin fragment 4–9 stimulates the acetylcholine release in hippocampus of freely-moving rats

We examined the effects of arginine-vasopressin (AVP) C-terminal fragment 4–9, which facilitates learning and memory, on the extracellular acetylcholine (ACh) release in hippocampus of freely-moving rats using the microdialysis technique. Following administration of AVP 4–9, p-Glu-Asn-Cys[Cys]-Pro-Arg-Gly-NH 2, through the dialysis probe into the hippocampus, ACh levels in dialysates from the hippocampus increased markedly in dose and time dependent manner at 2–2.5 and 2.5–3 hr. AVP 1–9, the parent 3eptide, has a similar enhancing effect on ACh release as AVP 4–9. Stimulated ACh released by AVP4–9 was significantly inhibited by V 1-selective receptor antagonist ([1-(β- mercapto-β,β-cyclopentamethylenepropionic acid), 2-(O-methyl)-tyrosine]AVP), but not by V 2-selective antagonist ([1-(β-mercapto-β,β-cyclopentamethylenepropionic acid), 2-D-Ile, 4-Ile]AVP). From these observations, it is demonstrated that AVP 4–9 stimulates the ACh release in rat hippocampus via mediating V 1-like vasopressin receptors.

O-105 - Neurochemical study of TA-0910. a new TRH analog (4): effect on acetylcholine release in rat hippocampus

O-105 - Neurochemical study of TA-0910. a new TRH analog (4): effect on acetylcholine release in rat hippocampus