Involvement of brain serotonergic function in lidocaine-induced convulsions in mice

Influences of drug-induced manipulations of central serotonergic function on lidocaine- and pentylenetetrazol (PTZ)-induced convulsions were examined in mice. Agents that suppressed serotonergic transmission increased, whereas drugs that facilitated serotonin (5-HT) function decreased the incidence of lidocaine-induced convulsions. These treatments had similar influences on the incidence of PTZ-induced convulsions. Lidocaine (10(-5)-10(-3) M) reduced the stimulation evoked [3H]5-HT release from cortical slices, followed with an increased spontaneous [3H] overflow at higher concentrations. These results may suggest that brain 5-HT neurons are causally involved as inhibitory neurons in lidocaine-induced convulsions as in the case of PTZ-induced convulsions.     

Synthesis of substituted anilino-3-methoxy-4-substituted acetoxy) benzylidenes and their monoamine oxidase inhibitory and anticonvulsant properties

Several substituted anilino-(3-methoxy-4-substituted acetoxy) benzylidenes were synthesized and characterized by their sharp melting points and elemental analyses. All substituted benzylidenes competitively inhibited the in vitro monoamine oxidase activity of rat brain homogenates and possessed anticonvulsant activity against pentylenetetrazol-induced convulsions in mice.     

Brain dopamine and seizure susceptibility in mice

In electroshock test apomorphine appeared without effect, D, L-amphetamine and L-DOPA (in a high dose) elevated the convulsive threshold, while amantadine decreased it. Among investigated dopamine (DA) receptor blockers spiperone, pimozide and fluphenazine lowered the threshold, haloperidol being without effect. The convulsive threshold elevated by L-DOPA was not affected by neuroleptics and phentolamine but on the other hand DA receptor blockers and phentolamine anatagonized the effect of D, L-amphetamine. The effect of amantadine was not influenced by neuroleptics. In pentylenetetrazol (PTZ) test only amantadine and L-DOPA (in high doses) affected the threshold, increasing seizure susceptibility; the above effect was not abolished by pimozide. Our results seem to indicate that the activity of brain DA system seems not to be involved directly in the susceptibility to electrogenic or PTZ-induced seizures in mice.     

Pharmacological analysis of local anaesthetic tolycaine-induced convulsions by modification of monoamines in rat brain

The effects of a local anaesthetic, tolycaine, on brain monoamine levels were investigated during the convulsive process in rats. The influence of central monoamine modifications on tolycaine-induced convulsions was also examined. Tolycaine (140 mg/kg, intraperitoneally) produced a significant elevation of noradrenaline and 5-hydroxytryptamine levels in all brain regions in the convulsive state from the levels in the non-convulsive state. Their levels returned to normal during the postconvulsive state. Dopamine levels were depleted in the cerebral cortex, the striatum, and the ponsmedulla oblongata during the convulsive process and increased in the cerebellum. Pretreatment with alpha-methyl-p-tyrosine, which depletes brain catecholamine, suppresses the tolycaine-induced convulsions, as shown by a decrease in the incidence; L-3,4-dihydroxyphenylalanine and bis-(1-methyl-4-homopiperazinyl-thiocarbonyl)-disulfide, which increase brain catecholamine, intensified the convulsions, as shown by shortening of the latency and increase in the mortality. Antagonists of beta-adrenergic and dopamine receptors, such as propranolol, chlorpromazine and pimozide, markedly suppressed the convulsions, but an antagonist of alpha-adrenergic receptor, phenoxybenzamine, had no effect. Furthermore, 5-hydroxytryptophan, which increases brain 5-hydroxytryptamine, suppressed the convulsions, and DL-p-chlorophenylalanine, which depletes brain 5-hydroxytryptamine, intensified them. Antagonists of 5-hydroxytryptamine receptor, methysergide and methiothepin, suppressed the convulsions. These results suggest that brain noradrenaline and 5-hydroxytryptamine are major regulators in the tolycaine-induced convulsive process and that central catecholaminergic neurones act in a stimulatory way on the tolycaine-induced convulsions, while serotonergic neurones act suppressively.     

Effect of anoxia on striatal monoamine metabolism in immature rat brain compared with that of hypoxia: an in vivo microdialysis study

We examined in 5-day-old rats the effects of either anoxia or 8% hypoxia on extracellular monoamines such as dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), 5-hydroxytryptamine (5-HT), and 5-hydroxyindole-3-acetic acid (5-HIAA) using in vivo microdialysis and subsequent HPLC. After stabilization 64 animals were exposed to 100% nitrogen for 16 min and 40 animals to 8% oxygen for 128 min. Both anoxia and hypoxia produced acute increase in the striatal extracellular DA (anoxia: P < 0.001, hypoxia: P < 0.01). Especially in anoxia, DA levels increased transiently to 2000-times the basal levels and 6-times higher than those in hypoxia. NE also increased in both anoxia and hypoxia. DOPAC and HVA decreased during hypoxia (P < 0.01 and P < 0.001, respectively), while those in anoxia were unchanged. In anoxia, decrease tendency of their levels were in short duration and that of 5-HIAA was followed by gradual increase (P < 0.001). These data demonstrated that brief exposure to anoxia or hypoxia had significant influence on striatal monoamine metabolism in immature brain and the pattern of change of monoamine in anoxia was different from that in hypoxia.     

Structure and expression of bombyxin E1 gene: a novel family gene that encodes bombyxin-IV, an insect insulin-related neurosecretory peptide

Comparison was made of the ability of two dihydropyridine calcium channel antagonists, nitrendipine and felodipine, to prevent a range of signs of ethanol withdrawal. The increases in handling-induced behavior seen in mice during withdrawal from chronic ethanol treatment were prevented by administration of nitrendipine, 50 mg/kg, but not by, felodipine, 10 mg/kg, a dose that caused a similar displacement of dihydropyridine binding in central nervous system tissue, in vivo and in vitro. A higher dose of felodipine, 20 mg/kg, also had no effects. Nitrendipine, but not felodipine, prevented audiogenic seizures during the withdrawal phase. Similarly, nitrendipine prevented both the decrease in thresholds for N-methyl-DL-aspartate seizures and the increase in thresholds for convulsions due to 4-aminopyridine, which were seen during the withdrawal period, while felodipine did not alter either of these changes. Withdrawal from the ethanol chronic treatment increased the thresholds to seizures produced by intravenous aminophylline; this change was also prevented by nitrendipine. The significance of this increase in thresholds was lost after felodipine administration. In naive mice (not treated with ethanol) the doses of nitrendipine and felodipine used in the withdrawal studies were tested against the effects of convulsant drugs. Both dihydropyridines increased, to similar extents, the thresholds for seizures produced by bicuculline, pentylenetetrazol, and by N-methyl-DL-aspartate. The thresholds for aminophylline were unaltered by either dihydropyridine. In contrast, the thresholds for seizures due to 4-aminopyridine in the naive animals were not changed by felodipine, but were increased by nitrendipine. The results suggest that changes in potassium, as well as calcium, may possibly be involved in some of the stages of the ethanol withdrawal syndrome.     

Lidocaine toxicity in primary afferent neurons from the rat

Evidence from both clinical studies and animal models suggests that the local anesthetic, lidocaine, is neurotoxic. However, the mechanism of lidocaine-induced toxicity is unknown. To test the hypothesis that toxicity results from a direct action of lidocaine on sensory neurons we performed in vitro histological, electrophysiological and fluorometrical experiments on isolated dorsal root ganglion (DRG) neurons from the adult rat. We observed lidocaine-induced neuronal death after a 4-min exposure of DRG neurons to lidocaine concentrations as low as 30 mM. Consistent with an excitotoxic mechanism of neurotoxicity, lidocaine depolarized DRG neurons at concentrations that induced cell death (EC50 = 14 mM). This depolarization occurred even though voltage-gated sodium currents and action potentials were blocked effectively at much lower concentrations. (EC50 values for lidocaine-induced block of tetrodotoxin-sensitive and -resistant voltage-gated sodium currents were 41 and 101 microM, respectively.) At concentrations similar to those that induced neurotoxicity and depolarization, lidocaine also induced an increase in the concentration of intracellular Ca++ ions ([Ca++]i; EC50 = 21 mM) via Ca++ influx through the plasma membrane as well as release of Ca++ from intracellular stores. Finally, lidocaine-induced neurotoxicity was attenuated significantly when lidocaine was applied in the presence of nominally Ca(++)-free bath solution to DRG neurons preloaded with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Our results indicate: 1) that lidocaine is neurotoxic to sensory neurons; 2) that toxicity results from a direct action on sensory neurons; and 3) that a lidocaine-induced increase in intracellular Ca++ is a mechanism of lidocaine-induced neuronal toxicity.     

Changes in brain monoamine neurotransmitter in iron deficiency nonanemic rats

An iron deficiency nonanemic rat model was established by feeding with low-iron diet (11.9 mg/kg) to study if there exists biochemical abnormality in brain tissues. Iron contents of the brain, activities of monoamine oxidase (MAO) in the corpus striatum, and the contents of monoamine neurotransmitter and its metabolite in the cerebral cortex and hippocampus were determined by DCP-AES technique, enzyme histochemical method, and high performance liquid chromatography with electrochemical detection (HPLC-ECD), respectively. Results showed that iron contents and activities of MAO in brain tissues of iron deficiency nonanemic rats reduced significantly, and contents of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) in cerebral cortex were significantly higher than those of controls, while 5-hydroxydroxytryptamine acid (5-HIAA) metabolite of 5-HT in the hippocampus was lower than that of controls. It indicated that there existed metabolic abnormality of monoamine neurotransmitter in the brain tissues of iron deficiency nonanemic rats. Also, this study laid a biochemical basis for abnormal mental and behavioral development caused by iron deficiency.     

Pediatric automotive restraints, pediatricians, and the academy

Behaviouristic and EEG-manifestations of pentylentetrazol convulsions were studied in unrestrained rats with preliminarily destroyed striatum. The operation caused no significant disturbance of the appearance of the spike-wave activity, but sharply inhibited provocation of myoclonic and their change into tonico-clonic convulsions. Besides, there was an increase in the threshold, the duration and the severity of the attack; an epileptic status was even observed in 50% of these rats. Striatectomy eliminated the action of catecholaminergic agents (apomorphine, DOPA, haloperidol, chlorpromazine) on the thresholds of myclonic jerks and the attack.     

Increase of striatal dopamine release by cadmium in nursing rats and its prevention by dexamethasone-induced metallothionein

Repeated daily intraperitoneal (i.p.) administrations of cadmium (CdCl2, 1 mg/kg per day for 5 days) increased striatal dopamine (DA) release (180% of controls) and turnover (150% of controls) in 13-day-old rats. Cd treatment also increased striatal metallothionein (MT) content (161%), Cd (127%) and lipid peroxidation (LPO, 190%). In addition, Cd treatment decreased striatal tyrosine hydroxylase (TH) activity (-28%), and such an effect may result from D-2 receptor blockade as a consequence of excessive dopamine release, since sulpiride (a specific D-2 receptor antagonist) administration to Cd-treated rats abolished the effect of Cd on TH. No effect was observed on striatal monoamine oxidase (MAO) activity. Dexamethasone (Dx) treatment increased striatal MT content and caused no effect on either DA release or turnover. However, Dx administration prevented the effects caused by Cd, including the increased DA release and enhanced striatal lipid peroxidation. These results indicate that toxic effects on the brain are to be expected as a result of Cd exposure and that Dx administration can attenuate them.     

Radiation sensitivity of lymphocytes from human blood and from the thoracic duct

Rats were cerebellectomized 72-96 hr prior to evaluation (1) during maximum electroshock seizures and (2) for their capacity to respond to pentylenetetrazol-induced clonic seizures. Cerebellectomized rats failed to exhibit tonic hindlimb extension, an endpoint characteristic of maximal electroshock seizures. The dose of pentylenetetrazol required to produce clonic seizures or death was not different in cerebellectomized and sham-operated controls. The anticonvulsant efficacy of diazepam, when assessed as a pentylenetetrazol antagonist, was not influenced by removal of the cerebellum. These data indicate that whereas cerebellar influences may suppress seizure activity which is largely focal, seizures of more diffuse origin are not markedly influenced by cerebellar activity. It is, therefore, essential that the role of the cerebellum in suppressing seizures be characterized for each kind of experimentally induced seizure process.     

Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies

The association of propofol with excitatory motor activity, such as myoclonic jerking and opisthotonus, in humans and in animals suggests that it may aggravate clinical seizure activity in some circumstances, although evidence suggests that under other circumstances, propofol inhibits seizure activity. In the current study, we assessed the effect of sedating doses of propofol on lidocaine-induced seizure activity in spontaneously breathing rats receiving no other anesthetics. Adult Sprague-Dawley male rats, 300-400 g, were divided into a control group and three experimental groups representing three graded levels of propofol sedation. The control rats then received a lidocaine infusion at the rate of 150 mg x kg(-1) x h(-1), resulting in a slow, progressive increase in systemic lidocaine concentrations. At the onset of electroencephalographic (EEG) seizure activity, arterial lidocaine concentrations were obtained. The treated rats received propofol according to three different dose schedules: Dose 1 = 10 mg x kg(-1) x h(-1) after a 2.5-mg/kg bolus; Dose 2 = 20 mg x kg(-1) x h(-1) after a 5-mg/kg bolus; Dose 3 = 40 mg x kg(-1) x h(-1) after a 10-mg/kg bolus. After 30 min, a steady level of sedation, dependent on the dose of propofol, was achieved. The lidocaine infusion was then started, and systemic lidocaine levels were obtained at the onset of EEG seizure activity. The lidocaine was continued until the onset of death by cardiac arrest. Plasma lidocaine was measured by gas chromatography. Analysis of variance and Dunnett's t-test were used for comparisons with the control values. Continuous propofol sedation increased the seizure dose of lidocaine from 37.7 +/- 3.5 mg/kg (mean +/- SEM) to 52.5 +/- 2.6 mg/kg (Dose 1, P < 0.05) and 67.9 +/- 8.6 mg/kg (Dose 2, P < 0.05), and completely abolished lidocaine seizures at Dose 3. The lethal dose of lidocaine, 89.4 +/- 10.5 mg/kg control versus 108.7 +/- 10.3 mg/kg (Dose 1), 98.3 +/- 10.1 mg/kg (Dose 2), and 93.5 +/- 10.4 mg/kg (Dose 3) did not differ among groups. The lidocaine levels at seizure threshold were increased in the propofol-treated rats: 16.9 +/- 0.5 microg/mL control versus 19.2 +/- 0.7 microg/mL (Dose 1, P = not significant) and 23.7 +/- 1.8 microg/mL (Dose 2, P < 0.05). Continuous propofol sedation in spontaneously breathing rats receiving no other anesthetics exerts a protective effect against lidocaine-induced seizures in a monotonic, dose-dependent fashion. The cardiac arrest dose of lidocaine is unaffected by propofol under these conditions. IMPLICATIONS: The i.v. anesthetic drug propofol, given to rats to produce sedation, was found to suppress seizure activity caused by overdosage of the local anesthetic lidocaine.     

Effect of N-methyl-D-aspartate and potassium on striatal monoamine metabolism in immature rat: an in vivo microdialysis study

Effects of N-methyl-D-aspartate (NMDA) and potassium on 5-day-old rat's brain were examined. We measured extracellular striatal monoamines such as dopamine (DA), 3,4 dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole-3-acetic acid (5-HIAA) using intracerebral microdialysis. After 3 h stabilization, pups received varying concentrations of NMDA (1-3 mM) and potassium (200-800 mM) by intrastriatal perfusion for 32 minutes. Increasing the concentration of NMDA and potassium induced a dose related DA increase (p < 0.001), whereas DOPAC, HVA, and 5-HIAA decreased significantly. Five days later the same animals were sacrificed and the weight reduction of their cerebral hemispheres was measured. The weight of the drug perfused side was significantly reduced compared with that of the contralateral one. We examined next the relationship between the level of maximum DA and the relative hemisphere weight reduction. The DA peak was highly correlated with the hemisphere weight reduction (r = 0.70, n = 52, p < 0.001 in the NMDA group, r = 0.83, n = 30, p < 0.001 in the potassium group, respectively). These data show that each treatment alter striatal monoamine metabolism in immature rat brain and that the extracellular DA peak is a potential early indicator to estimate brain injury.     

Reduced striatal tyrosine hydroxylase activity is not accompanied by change in responsiveness of dopaminergic receptors following chronic treatment with deprenyl

Deprenyl is the only selective monoamine oxidase B (MAO-B) inhibitor that is in clinical use for the treatment of Parkinson's disease. Our previous studies showed that chronic treatment of rats with low (MAO-B selective) doses of deprenyl inhibited dopamine (DA) re-uptake and enhanced DA release in the striatum. These changes could affect DA synthesis rate by activation of negative feedback loops. Chronic deprenyl treatment has also been suggested to cause down-regulation of release-modulating DA receptors. The effects of chronic and acute treatment with deprenyl on ex vivo striatal tyrosine hydroxylase activity were therefore studied, by determination of steady-state tissue level of DOPA following administration of NSD-1015 (100 mg/kg i.p.). In addition, we assessed changes in the in vivo sensitivity of dopaminergic receptors from the reduction in DOPA extracellular level after systemic apomorphine administration (2.5 mg/kg s.c.), following elevation of microdialysate DOPA by systemic or local aromatic amino acid decarboxylase inhibition with NSD-1015. Chronic treatment with deprenyl (0.25 mg/kg s.c. daily for 21 days) caused a significant reduction in tyrosine hydroxylase activity to 60% of control, with no change in the apomorphine-induced reduction of microdialysate DOPA and DOPAC. The reduction in tyrosine hydroxylase activity is compatible with our previous results showing an increase in striatal DA extracellular level following chronic treatment with deprenyl. The increased extracellular striatal DA level could reduce tyrosine hydroxylase activity through activation of a negative feedback loop, by activation of either presynaptic or postsynaptic DA receptors.     

Effects of repeated injection of cyclosporin A on pentylenetetrazol-induced convulsion and cyclophilin mRNA levels in rat brain

To investigate the relationship between the immune system and convulsions in an animal model, we examined the effects of repeated administration with the immunosuppressant cyclosporin A on pentylenetetrazol (PTZ)-induced convulsions and the changes in the mRNA expression of its binding protein cyclophilin in the rat brain. The consecutive administration of cyclosporin A (5 mg/kg, s.c., 14 days) significantly aggravated the severity of convulsions induced with PTZ 75 mg/kg, i.p. Furthermore, it down-regulated the levels of cyclophilin mRNA in several brain regions and inhibited the PTZ-induced increase of hippocampal cyclophilin mRNA. Compared with the group without PTZ pretreatment or the group treated with chronic vehicle administration after the PTZ-preinjection, chronic cyclosporin A administration after the initial injection of PTZ apparently aggravated convulsions after the second PTZ injection. Interestingly, the increase in hippocampal cyclophilin mRNA observed after a single PTZ injection was not found after the second PTZ injection in the group with PTZ pretreatment. Therefore, these findings suggest that cyclosporin A administered peripherally can affect the central nervous system, and that an immune response associated with the first convulsive episode plays a key role in severity during subsequent attacks.     

Age-related changes in cerebral and peripheral monoamine contents in stroke-prone spontaneously hypertensive rats

1. We examined monoamine contents in various regions of the brain and catecholamine contents in the heart and the adrenal gland of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats aged 1.5, 3 and 6 months. 2. The noradrenaline (NA) content and the 5-hydroxytryptamine (5-HT) content in the brainstem were larger in 1.5 month old SHRSP than in the age-matched WKY. In addition, at age 6 months the brainstem 5-HT content was higher in SHRSP than in WKY. 3. The NA and 5-HT contents in basal ganglia, thalamus, hypothalamus, septum and anterior and lateral cerebral cortex showed no significant difference between SHRSP and WKY at any age. 4. The dopamine (DA) contents in all brain regions examined did not differ between WKY and SHRSP at any age. 5. The NA contents in left and right ventricles were larger in 3 month old SHRSP than in the age-matched WKY, but were lower in 6 month old SHRSP than in the age-matched WKY. The cardiac DA contents did not differ between the two rat strains of any age. 6. The adrenal NA and adrenaline (A) contents in 6 month old SHRSP were significantly larger than those in the corresponding WKY. 7. These findings suggest that the increased NA and 5-HT contents in the brainstem may be related to the onset of hypertension, and that the altered cardiac NA contents and adrenal NA and A contents change as a result of the onset or persistence of hypertension.     

Clinical utility of plasma membrane vesicles expressing recombinant glycophorin A-encoded blood group antigens

Siotone granule, a herbal psychotropic formulation was tested for its effectiveness in various models of convulsions in animals. S. granule (100 and 200 mg/kg) offered significant protection against pentylenetetrazol-, maximal electroshock- and strychnine-induced convulsions. In hypoxic stress-induced convulsions only 200 mg/kg was effective. It also reduced percent mortality per se and rendered total protection when given in combination with sub-protective dose of diazepam (0.5 mg/kg) and MK-801 (0.1 mg/kg) against pentylenetetrazol-induced convulsions. The anticonvulsant action of S. granule was blocked by flumazenil (4 mg/kg) suggesting the involvement of GABAergic mechanism.     

The effect of soup on satiation

During postnatal brain development, the function of Na+ channels undergoes changes. We investigated at the single channel level whether the lidocaine sensitivity of the open state of brain Na+ channels changed during development and the underlying kinetic differences of the lidocaine-induced open channel block between brain and muscle Na+ channels. The lidocaine affinity for the open channel state was found to be about 30% higher in 15 day old than in newborn channels and reflected a higher binding rate constant in 15 day old channels. When compared with reported values from adult muscle Na+ channels, lidocaine blocked the open state of brain channels with about ten times higher potency and reflected a lower unbinding rate constant in brain channels. These results indicate that the conformations of the channel structures defining the lidocaine accessibility to its binding site must undergo changes during brain development and that the conformations of the channel structures interacting with lidocaine must be different in brain and muscle channels.     

Anticonvulsant efficacy of L-deprenyl (selegiline) during chronic treatment in mice: continuous versus discontinuous administration

We have previously reported that L-deprenyl (selegiline), an irreversible inhibitor of monoamine oxidase type B (MAO-B), exerts anticonvulsant activity against different seizure types in mice and rats. The anticonvulsant effect of L-deprenyl was rapid in onset but short lasting, arguing in favor of other, reversible mechanisms of L-deprenyl as a basis for the anti-seizure activity. For further evaluation, we administered L-deprenyl continuously via subcutaneously implanted osmotic minipumps in mice and determined the threshold for myoclonic seizures induced by i.v. infusion of pentylenetetrazol repeatedly during prolonged treatment, with treatment periods lasting from 2 to 4 weeks. For comparison with continuous administration via minipumps, L-deprenyl was injected once daily at a dose (10 mg/kg) known to produce complete and irreversible inhibition of MAO-B and anticonvulsant effects after acute administration in rodents. Continuous administration of L-deprenyl, 50 or 100 mg/kg per day, led to a progressive increase in seizure threshold in the absence of any observable adverse effects, while administration of 10 mg/kg per day via minipumps was devoid of any significant anticonvulsant effect. When 10 mg/kg were administered once daily in the afternoon for 4 weeks and the seizure threshold was determined repeatedly in the morning, no significant anticonvulsant effect was observed. The data argue against a critical role of MAO-B inhibition in the anticonvulsant activity of L-deprenyl but suggest that other, reversible biochemical and cellular effects known to occur at higher doses of this drug are involved in this respect. In view of the short half-life of L-deprenyl, these reversible effects can only be maintained during chronic treatment when the drug is given continuously such as via implanted minipumps.     

Altered sensitivity to footshock after selective serotonin depletion: Comparison of electrolytic lesions and neurotoxin injections in the medial forebrain bundle of the rat.

Compared the changes in 183 male albino rats' jump threshold with changes in monoamine content of the telencephalon after damage to the lateral hypothalamus produced either by electrolytic lesions or by 6-hydroxydopamine (6-OHDA) and 5,7-dihydroxytryptamine (DHT). Electrolytic lesions produced significant decreases in jump threshold and in telencephalic content of serotonin, norepinephrine, and dopamine. Infusions of DHT, with or without pretreatment with desipramine, always reduced both jump thresholds and serotonin content, even when there was no effect on norepinephrine or dopamine. In contrast, 6-OHDA had no effect on jump thresholds or serotonin content, even though both norepinephrine and dopamine were greatly reduced. Results suggest that the increased sensitivity to footshock was solely due to the interruption of ascending serotonergic pathways within the lateral hypothalamus and was not a result of damage either to norepinephrine and dopamine pathways or to some other neural system. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)