Biosynthesis of brain 2-phenylethylamine: influence of decarboxylase inhibitors and D-amphetamine

2-Phenylethylamine (PEA) is an endogenous brain amine which probably modulates affective behavior. Using a gas-liquid chromatographic method for the quantification of PEA (as its dinitrophenyl-sulfonic acid derivative), we found in rabbits 340.9 ± 45.8 ng of PEA/g of wet brain. Brain PEA levels were markedly decreased by the ip administration of 200 mg/Kg, 4 hrs before sacrifice, of the L-aromatic amino acid decarboxylase inhibitors α-methyldopa (28.2 ± 5.1 ng/g), L-α-methyldopa hydrazine (MK-486 [66.9 ± 13.0 ng/g]) or a combination of both (30.0 ± 3.3 ng/g). Since MK-486 inhibits only peripheral decarboxylase, brain PEA must be in part of peripheral origin. Another decarboxylase inhibitor, RO 4-4602 mg/Kg, 4 hrs before sacrifice) failed to affect brain PEA content. D-amphetamine (10 mg/Kg) induced a small depletion of PEA after 30 min in untreated animals; when given in combination with RO 4-4602, brain PEA content was markedly decreased. This supports the view that amphetamine releases PEA and stimulates its synthesis.     

Interactions of taurine and beta-alanine with central nervous system neurotransmitter receptors

Varying amounts of labeled phenylethylamine (PEA), ptyramine (TRM) and phenylacetic acid (PAAc) were recovered from rabbit brain homogenates at different intervals after the intraventricular (ivn) administration of either labeled L-phenylalanine or PEA. Previous administration of imipramine or amphetamine decreased the recoveries of PEA and PAAc. Imipramine increased the recovery of TRM, which was not affected by amphetamine. The ivn injection of TRM, 2, 5, 10 and 20 min before sacrifice resulted in the recoveries of decreasing amounts of PEA. Pretreatment of the animals with chlorpromazine, haloperidol or smaller doses of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) did not affect PEA recoveries from brain homogenates, whereas amphetamine or larger Δ⁹-THC doses resulted in increased and decreased PEA yields, respectively.These studies further show the existence of an $\text{in}$$\text{vivo}$ brain metabolic pathway linking L-phenylalanine to PEA and TRM. It also shows that these pathways are modified by a number of centrally active drugs.     

Putrescine has hypothermic and antipyretic activity, in rats

Intraperitoneal injection of putrescine induced dose-related hypothermia in rats. The effect was more pronounced at room temperature (22 degrees C) than in a warm environment (30 degrees C), the maximum hypothermia (-2.64 +/- 0.29 degrees C, 30 min. after treatment) being obtained with the dose of 300 mg/Kg and remaining significant throughout 3 hr of observation. Putrescine also had antipyretic activity, as it significantly reduced pyrogen-induced fever at a dose level (100 mg/Kg i.p.) ineffective in causing hypothermia in normal rats. The hypothermic and antipyretic effects of putrescine were not associated with any obvious sign of toxicity.     

Analgesic Effects of β-Phenylethylamine and Various Methylated Derivatives in Mice

Administration of β-phenylethylamine (PEA), the simplest endogenous neuroamine, and various methylated PEA derivatives including α-methyl PEA (amphetamine, AMP) elicits analgesia in mice. Five or 20 min after intraperitoneal PEA injection of as little as 6 mg/kg resulted in an increased latency response time (from 2.4 ± 0.4 to 8.5 ± 2.3 or 7.0 ± 3.0 s, respectively) to the thermal stimulus (hot-plate test), which reached statistical significance at the 15 mg/kg (20 min; 13.1 ± 0.4 s) or 25 mg/kg dose (5 min; 15.3 ± 4.1 s). This PEA effect, was dose-dependent (albeit non-linear: 6, 12, 15, 25, 50 and 100 mg/kg), reached the cut-off time of 45 s at the upper PEA dose (5 min), and it was consistently enhanced by pretreatment with the monoamine oxidase inhibitor pargyline (P). Methylated PEA derivatives (15 and 100 mg/kg dose) produced various degrees of analgesia (in decreasing order p-Me PEA > PEA > N,N-diMe PEA > N-Me PEA) which, likewise to PEA itself, were consistently increased by P and declined over time (mice tested 5, 20 and 60 min after amine injection); small but statistically significant o- and β-Me PEA antinociceptive effects (5 min) were observed only at the higher dose (in the presence of P for β-Me PEA). A small analgesic effect was observed after the administration of AMP (5 or 10 mg/kg) which failed, even after P, to reach statistically significance. Independent of the amine and concentration tested, individual compound’s antinociceptive properties were reliably increased by P (exception of AMP), decreased by reserpine (R) or haloperidol (H), and remained essentially unchanged after naloxone (N) administration suggesting the involvement of catecholamines, but not opioid peptides, in their observed analgesic effects. Injection of P + N produced results similar to those seen after P alone. Under the experimental conditions described neither P, R, H or N had any effects by themselves. These findings suggest additional understanding of the mechanism of action responsible for the analgesic effects of these amines would be of interest, leading further to controlled studies on their alleged usefulness as weight reducing agents and sport performance enhancers.     

Oxytocin acts as an antidepressant in two animal models of depression

In the behavioral despair test in mice, oxytocin, i.p. injected 60 min before testing, significantly reduced the duration of immobility at doses of 0.250-1.0 mg/Kg; the effect being similar to that of imipramine (7.5-30 mg/Kg i.p.). A more powerful effect was obtained with a 10-day treatment schedule. In the learned helplessness test, oxytocin (0.500 mg/Kg/day i.p. for 8 days) significantly reduced the escape failures and the latency to escape, the effect being even more intense than that of imipramine (20 mg/Kg/day i.p. for 8 days). These results show a new behavioral effect of oxytocin, and further support its role of CNS regulatory peptide.     

IMmunosuppressants and TGF-β1 accelerated and prolonged the nitric oxide/oxyradicals-dependent suppression by dexamethasone in paw edema of mice

Dexamethasone (Dex, 0.3 mg/Kg, S.c.) did not suppress histamine and ischemic paw edema of mice up to 1 hr. However, given TGF-β1 (0.3 μ g/Kg, I.p.), Dex suppression appeared early as 30 min (36% and 42%). When Dex (0.1 mg/Kg, S.c.) was injected 6 hr before the assay, Dex alone, TGF-β1 ± Dex, FK506 (10 mg/kg, oral)± Dex, cyclosporin A (CsA, 30 mg/kg, oral) ± Dex, rapamycin (Rapa, 10 mg/Kg, I.p.) ± Dex, deoxyspergualin (DSP, 10 mg/Kg, I.p.) ± Dex, did not suppress the edemata (less than 11 %). Nevertheless, if Dex and TGF-β1 were dosed together with one of these immunosuppressants, suppressions of histamine and ischemic edema were 53%, 45% (FK506), 45%, 49% (CsA), 44%, 48% (Rapa) and 39%, 51% (DSP), respectively. Glucocorticoid (GC) receptor (GR) complex contains heat shock proteins such as hsp56 (or CsA-binding protein: CyP-40), hsp70 and hsp90. FK506, Rapa and TGF-β1 receptor I (TR-I) bind FK-binding protein-12 (FKBP-12). FK506 and Rapa bind also hsp56. CsA binds CyP-40. DSP binds hsp70 and/or hsp90. These bindings might change or stabilize the conformation of GR complex resulting in edema suppressions. Nitric oxide synthase (NOS) inhibitors, superoxide dismutase (SOD), catalase, mannitol and cycloheximide, reversed the edema suppressions by TGF-β1 ± immunosuppressant at 30 min and 6 hr after Dex. Endogenous NO, Or and/or · OH seemed to be essential for edema suppressions. Our demonstration in vivo may offer a theoritical support for clinicians to adopt combination therapy of immunosuppressant(s) and GC.     

Amphetamine-induced inhibition of central noradrenergic neurons: a pharmacological analysis

The amphetamine-induced inhibition of brain noradrenaline (NA) containing neurons in the rat locus coeruleus (LC) was pharmacologically analyzed utilizing single unit recording techniques. The presynaptic α-receptor blocking agent yohimbine (10 mg/kg i.p., 30 min before) largely prevented the amphetamine-induced depression of LC units in contrast to prazosin (0.6 mg/kg i.p., 30 min) or phenoxybenzamine (20 mg/kg, 30 min) which both slow preference for postsynaptic α-receptors. The β-receptor blocking agent, propranolol (10 mg/kg, 30 min), as well as the peripherally but not centrally active α-receptor blocking drug phentolamine (10 mg/kg, i.p., 30 min), also did not block the amphetamine effect. The LC inhibition by amphetamine was blocked by pretreatment with reserpine (10 mg/kg, i.p., 5 h), which caused almost total depletion of brain catecholamines. However, unlike the amphetamine-induced inhibition of central dopamine (DA) neurons the NA cell inhibition was not blocked by pretreatment with a tyrosine hydroxylase inhibitor (α-MT, 50 or 250 mg/kg i.p., 30 min). These results suggest that the amphetamine-induced inhibition of NA neurons in the LC is an indirect effect, mediated via activation of central α-receptors of presynaptic character. The lack of antagonism by α-MT indicate that the NA release by amphetamine, unlike its effect on brain DA, is not critically dependent on the rate of tyrosine hydroxylation. Thus the euphoriant action of amphetamine, which is blocked by α-MT, may be associated with release of DA rather than NA in brain.     

Constipating and spasmolytic effects of Khat (Catha edulis Forsk) in experimental animals.

The constipating and spasmolytic effects of Catha edulis Forsk (Khat) were investigated in whole mice and on isolated guinea pig ileum. D-amphetamine was employed in both experiments for comparison. The total distance travelled (expressed in percentage) by charcoal suspension in the gastrointestinal tract of mice was determined before and after khat administration. The procedure was repeated with amphetamine and normal saline. The results were compared. Amplitudes of contraction were recorded with standard spasmogens, histamine and carbachol, in the presence and absence of khat extract of different concentrations. The same was done with amphetamine. Khat extract was observed to reduce the total distance travelled by charcoal suspension, comparable to D-amphetamine. The spasmogenic effects of both histamine and carbachol were observed to be antagonized by the khat extract in a concentration-dependent manner. The antispasmodic effect of khat extract was observed to be similar to that of D-amphetamine.     

EFFECT OF γ-AMINOBUTYRIC ACID ON BRAIN SEROTONIN AND CATECHOLAMINES

—Intraperitoneal injections of GABA (5 mg/kg) to rats lowered the level of norepinephrine in brain, heart and spleen but not suprarenals and raised that of serotonin in brain. Changes of these monoamines were most pronounced in the hypothalamic region after 20min. A reduction of hypothalamic norepinephrine was also observed 15min following the intracarotid administration of 0·5 mg/kg of GABA. In these experiments there was a concomitant increase in the level of free GABA in the anterior portion of the ventral hypothalamus. Brain dopamine level and 5-hydroxytryptophan decarboxylase, dihydroxyphenylalanine decarboxylase and monoamine oxidase activities were not affected. The 20 per cent increase of endogenous GABA observed in the midbrain 30 min following the administration of amino-oxyacetic acid was accompanied by a sharp fall in norepinephrine level (39 per cent) and an increase in serotonin (20 per cent). In in vitro studies 10–300 μg/ml of GABA were shown to release norepinephrine from cortical and hypothalamic slices, and to inhibit serotonin release without affecting 5-hydroxytryptophan uptake and to have no effect on the release of dopamine from slices of the region of the corpus striatum nor on the activity of the enzymes mentioned. Subcellular studies showed that the particulate:supernatant ratio for norepinephrine was reduced from a control value of 2·04 to 1·75 and that of serotonin was raised from 2·8 to 3·5. Following pretreatment with iproniazid, GABA reduced the raised level of brain norepinephrine to a greater extent than reserpine but not as intensively as amphetamine. The results obtained suggest that these monoamines may be involved in the mechanisms underlying the action of GABA in brain and that the effect of GABA on brain monoamines may be of certain significance in synaptic events.     

Further evidence for a role of 2-phenylethylamine in the mode of action of delta 9-tetrahydrocannabinol

In rabbits, Δ⁹-tetrahydrocannabinol (Δ⁹-THC) increased the recovery of labeled 2-phenylethylamine (PEA) from brain following its intraventricular administration. Δ⁹-THC also enhanced the excitatory effect of iontophoretic PEA on cortical unit potentials. Although Δ⁹-THC induced sedation in mice, the subsequent injection of reserpine induced transient excitement. Low doses of PEA, which do not significantly alter the behavior of mice, induced marked excitement in mice pretreated with Δ⁹-THC. In mice treated with pargyline, Δ⁹-THC induced excitement (instead of sedation); this excitement was increased by PEA and reduced by phenylethanolamine. These results suggest that Δ⁹-THC inhibits the disposition of PEA. Since endogenous PEA may be one of the adrenergic ergotropic modulators, it may play a role in the euphoriant effect of marihuana.     

微波辐射对小鼠脑内乙酰胆碱含量及胆碱乙酸转移酶活性的影响

用频率为2450MHz功率密度为10mW/Cm~2(WBASAR约11.4W/kg)的微波(连续波)对置于微波暗室内的昆明种雄性小鼠急性全身照射1小时后,立即按常规方法断头,取脑,制成样品,然后用放射免疫测定法测量小鼠脑内乙酰胆碱(ACh)含量及胆碱乙酰转移酶(ChAT)活性。结果表明:照射组的ACh含量为11.6±1.4pmol/mg(脑鲜重),ChAT活性为45.4±8.7pmolACh/min.mg(脑鲜重);而对照组的分别为16.0±2.1pmol/mg和61.0±13.8pmolACh/min.mg。证明微波照射后可引起动物脑内ACh水平和ChAT活性下降,提示微波辐射对中枢胆碱能系统确有不利影响。     

IN VIVO EFFECTS OF AMPHETAMINE ON METABOLITES AND METABOLIC RATE IN BRAIN

—The concentrations of several metabolites, including glucose, glycogen, glucose-6-phosphate, lactate, ATP and phosphocreatine have been measured in the brains of mice rapidly frozen at various intervals after the intraperitoneal injection of d -amphetamine sulphate (5 mg/kg). During the initial 30 min following injection, amphetamine induced a fall in cerebral glycogen and phosphocreatine and an elevation of lactate. Changes in glucose and brain/blood glucose ratios were less marked over this period. The metabolite levels returned to control values at 60 min. The cerebral metabolic rate calculated by the ‘closed system’ technique also showed a biphasic change. An initial depression of energy flux over the first 15 min following amphetamine injection was followed by an increase that appeared to be closely associated with the increase in locomotor activity over this period. The results have been discussed in relation to the known catecholamine-releasing action of amphetamine, and differential effects on glial cells and neurons have been proposed.     

Protective effect of Crocus sativus stigma extract and crocin (trans-crocin 4) on methyl methanesulfonate-induced DNA damage in mice organs

This study was designed to examine the effect of aqueous extract of Crocus sativus stigmas (CSE) and crocin (trans-crocin 4) on methyl methanesulfonate (MMS)-induced DNA damage in multiple mice organs using the comet assay. Adult male NMRI mice in different groups were treated with either physiological saline (10 mL/Kg, intraperitoneal [ip]), CSE (80 mg/Kg, ip), crocin (400 mg/Kg, ip), MMS (120 mg/Kg, ip), and CSE (5, 20, and 80 mg/Kg, ip) 45 min prior to MMS administration or crocin (50, 200, and 400 mg/Kg, ip) 45 min prior to MMS administration. Mice were sacrificed about 3 h after each different treatment, and the alkaline comet assay was used to evaluate the effect of these compounds on DNA damage in different mice organs. The percent of DNA in the comet tail (% tail DNA) was measured. A significant increase in the % tail DNA was seen in nuclei of different organs of MMS-treated mice. In control groups, no significant difference was found in the % tail DNA between CSE- or crocin-pretreated and saline-pretreated mice. The MMS-induced DNA damage in CSE-pretreated mice (80 mg/Kg) was decreased between 2.67-fold (kidney) and 4.48-fold (lung) compared to those of MMS-treated animals alone (p < 0.001). This suppression of DNA damage by CSE was found to be depended on the dose, which pretreatment with CSE (5 mg/Kg) only reduced DNA damage by 6.97%, 6.57%, 7.27%, and 9.90% in liver, lung, kidney, and spleen, respectively (p > 0.05 as compared with MMS-treated group). Crocin also significantly decreased DNA damage by MMS (between 4.69-fold for liver and 6.55-fold for spleen, 400 mg/Kg), in a dose-dependent manner. These data indicate that there is a genoprotective property in CSE and crocin, as revealed by the comet assay, in vivo.     

Amphetamine-induced locomotor behavior of mice is influenced by DSIP

The delta sleep-inducing peptide (DSIP) has been shown to induce effects other than only delta sleep. One of these effects was the paradoxical thermoregulatory and locomotor response of rats to amphetamine after DSIP administration. In the present investigation we found similar effects of DSIP on the locomotor activity in mice. However, two different doses of DSIP (30 and 120 nmol/kg) and 3 doses of amphetamine (4, 10, and 15 mg/kg) produced a complex pattern of effects in mice tested at 22 degrees C. In general, DSIP-treated mice showed lower locomotor activity after amphetamine than controls, but under two conditions, both using 15 mg/kg amphetamine, DSIP produced higher scores; this occurred in the first two hours after amphetamine for the 30 nmol/kg DSIP group and in the third hour for mice given 120 nmol/kg DSIP. The results indicate that the effects of DSIP on locomotor behavior were dependent on the dosage of the peptide and the time of measurement as well as the level of amphetamine stimulation.     

The novel nociceptin/orphanin FQ receptor antagonist Trap‐101 alleviates experimental parkinsonism through inhibition of the nigro‐thalamic pathway: positive interaction with L‐DOPA

In this study we investigated whether the recently discovered antagonist of the nociceptin/orphanin FQ (N/OFQ) opioid peptide (NOP) receptor, 1‐[1‐(cyclooctylmethyl)‐1,2,3,6‐tetrahydro‐5‐(hydroxymethyl)‐4‐pyridinyl]‐3‐ethyl‐1,3‐dihydro‐2H‐benzimidazol‐2‐one (Trap‐101) changed motor activity in naïve rats and mice, and alleviated parkinsonism in 6‐hydroxydopamine hemilesioned rats. In naïve rats, Trap‐101 stimulated motor activity at 10 mg/Kg and inhibited it at 30 mg/Kg. Such dual action was also observed in wild‐type but not NOP receptor knockout mice suggesting specific involvement of NOP receptors. Trap‐101 alleviated akinesia/bradykinesia and improved overall gait ability in hemiparkinsonian rats, being effective starting at 1 mg/Kg and without worsening motor deficit at 30 mg/Kg. To investigate the circuitry involved in the Trap‐101 action, behavioral tests were performed in rats undergoing microdialysis. The anti‐akinetic/anti‐bradykinetic effects of Trap‐101, given systemically (10 mg/Kg) or perfused in substantia nigra reticulata (10 μM), were associated with reduced glutamate and enhanced GABA release in substantia nigra, and reduced GABA release in ipsilateral ventro‐medial thalamus. When combined with ineffective doses of l ‐DOPA (0.1 mg/Kg), Trap‐101 evoked larger neurochemical and behavioral responses. These data show that Trap‐101 is an effective NOP receptor antagonist in vivo and confirm that NOP receptor antagonists alleviate parkinsonism through blockade of nigral NOP receptors and impairment of nigro‐thalamic transmission.     

MAO activity in serotonergic endings of rat major cerebral arteries

The present work studies the existence of monoamine oxidase (MAO) activity in serotonergic endings present in rat major cerebral arteries. Enzymatic activity was appraised in vivo by serotonin (5-HT) accumulation or 5-hydroxyindole acetic acid (5-HIAA) disappearance with time after systemic administration of MAO inhibitors. Pargyline (75 mg/Kg, ip) brought about significant 5-HT increase and 5-HIAA decrease in major cerebral arteries 30 and 60 min after its administration. Clorgyline (75 mg/Kg, ip) also induced 5-HT enhancement and 5-HIAA decline in these arteries 30 and 60 min after its injection. However, treatment with deprenyl (75 mg/Kg, ip) only evoked a significant 5-HT increase at 60 min. When either clorgyline (5 mg/Kg, ip) or deprenyl (5 mg/Kg, ip) were administered 5-HT and 5-HIAA levels remained unaffected. Two weeks after performing electrolytical lesion of dorsal raphe nucleus and 60 min after clorgyline (75 mg/Kg, ip) injection 5-HT and 5-HIAA levels appeared significantly reduced in cerebral arteries and striatum when compared to sham-lesioned controls. These results suggest that MAO-A isoform acting on endogenous 5-HT is present in rat major cerebral arteries and is located in nerve endings of fibers arising from dorsal raphe nucleus.     

The effect of S-adenosyl-l-methionine on ischemia-induced disturbances of brain phospholipid in the gerbil

Brain ischemia was produced in gerbils (Meriones unguiculatus) by the bilateral ligation of the carotid arteries with reported procedures. Changes in the energy status of brain demonstrated that carotid ligation was effective. At different time intervals from ligation, groups of gerbils were given either saline of S-Adenosyl-L-methionine (SAMe) by the intraventricular (i.v.) route (1.6 mg/Kg body wt. twice, at each 10 min interval), or by the intraperitoneal (i.p.) administration (200 mg/Kg body wt.) or subcutaneously (s.c.) with 40 mg/Kg body wt, daily, for two weeks. Control animals, with and without SAMe, together with the ischemic groups, were decapitated directly into liquid nitrogen, 10 min after ligation. Brain neutral and polar lipid, together with free fatty acids, which were all labeled in vivo by the intraventricular injection of [1-14C]arachidonic acid 2 hr prior to ligation, were extracted, purified and separated by conventional procedures. SAMe when injected i.v. or i.p. noticeably corrected the changes in polar lipid by reversing the decrease of brain phosphatidylcholine and choline plasmalogen, as well as of their labeling, which was due to ischemia. Concurrently with this action, SAMe treatment (i.v. and i.p.) also provided to some extent to re-establish the normal level of labeling of ethanolamine lipids. When SAMe was given s.c., no effect was present. SAMe had no effect on the increase of free fatty acid and diglyceride due to ischemia. The prevention by SAMe of the changes of choline lipids suggests that a stimulation of the methyltransferase reaction may occur in the ischemic brain, due to increased substrate (SAMe) availability. This effect may be important for cell survival, since membrane phospholipid derangements alter the properties of the membrane.     

The enigma of conditioned taste aversion learning: stimulus properties of 2-phenylethylamine derivatives

The functional aversive stimulus properties of several IP doses of (+/-)-amphetamine (1.25-10 mg.kg-1), 2-phenylethylamine (PEA, 2.5-10 mg.kg-1, following inhibition of monoamine oxidase with pargyline 50 mg.kg-1) and phenylethanolamine (6.25-50 mg.kg-1) were measured with the conditioned taste aversion (CTA) paradigm. A two-bottle choice procedure was used, water vs. 0.1 % saccharin with one conditioning trial and three retention trials. (+/-)-Amphetamine and phenylethanolamine induced a significant conditioned taste aversion but PEA did not. (+/-)-Amphetamine and PEA increased spontaneous locomotor activity but phenylethanolamine had no effects on this measure. Measurement of whole brain levels of these drugs revealed that the peak brain elevation of PEA occurred at approximately 10 min whereas the peak elevations of (+/-)-amphetamine and phenylethanolamine occurred at approximately 20 min. The present failure of PEA to elicit conditioned taste aversion learning is consistent with previous reports for this compound. The differential functional aversive stimulus effects of these three compounds are surprising since they exhibit similar discriminative stimulus properties and both (+/-)-amphetamine and PEA are self-administered by laboratory animals. The present data suggest that time to maximal brain concentrations following peripheral injection may be a determinant of the aversive stimulus properties of PEA derivatives.     

Acetaminophen: antipyretic or hypothermic in mice? In either case, PGHS-1b (COX-3) is irrelevant

Acetaminophen (AC) reduces the core temperatures (T(c)) of febrile and non-febrile mice alike. Evidence has been adduced that the selectively AC-sensitive PGHS isoform, PGHS-1b (COX-3), mediates these effects. PGHS-1b, however, has no catalytic potency in mice. To resolve this contradiction, AC was injected intravenously (i.v.) into conscious PGHS-1 gene-sufficient (wild-type (WT)) and -deficient (PGHS-1(-/-)) mice 60 min before or after pyrogen-free saline (PFS) or E. coli LPS (10 microg/kg) i.v. T(c) was monitored continuously; brain and plasma PGE(2) levels were determined hourly. AC at <160 mg/kg did not affect T(c) when given before PFS or LPS; at 160 mg/kg, it caused a approximately 2.5 degrees C T(c) fall in 60 min. LPS given after AC (all doses) induced a approximately 1 degrees C fever, not different from that in AC-untreated mice. But this rise was insufficient to overcome the hypothermia of the 160 mg/kg-treated mice; their T(c) culminated 1 degrees C below baseline. LPS given before AC similarly elevated T(c) approximately 1 degrees C. This rise was reduced to baseline in 30 min by 80 mg AC/kg; T(c) rebounded to its febrile level over the next 30 min. At 160 mg/kg, AC reduced T(c) to 4 degrees C below baseline in 60 min, where it remained until the end of the experiment. WT and PGHS-1(-/-) mice responded similarly to all the treatments. The basal brain and plasma PGE(2) levels of PFS mice and the elevated plasma levels of LPS mice were unchanged by AC at 160 mg/kg; but the latter's brain levels were reduced at 1h, then recovered. Thus, AC could exert an anti-PGHS-2 effect when this enzyme is upregulated in the brain of febrile mice. The hypothermia it induces in non-febrile mice, therefore, is due to another mechanism. PGHS-1b is not involved in either case.     

Effect of thiopental sodium and barbitone sodium on the total acetylcholine content and acetylcholinesterase activity in the brain tissue of Arvicanthis niloticus

The total ACh content and AChE activity were determined 1 hr after the i.p. injection of different doses of thiopental sodium (5, 10 and 20 mg/ml/100 g body wt) and barbitone sodium (20, 40 and 80 mg/ml/100 g body wt). The effect of different time intervals (1 min, 10 min, 30 min, 1 hr, 2.5 hr, 5 hr, 8 hr, 12 hr, 24 hr and 48 hr) on the total ACh content and AChE activity was investigated after i.p. injection of 10 mg thiopental sodium and 40 mg barbitone sodium/ml/100 g body wt. Both thiopental sodium and barbitone sodium increased the total ACh content in the brain tissue of Arvicanthis niloticus. Both drugs inhibited the brain AChE activity. It is thought that the increase in the total ACh content in the brain tissue of Arvicanthis niloticus may be due to a decrease in the release of ACh from the neuronal tissue and a decrease in AChE activity.