SEARCH · PubMed Health

Results for “PICROTOXIN”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources

PubMed1970

Central effects of picrotoxin when acting from the liquor spaces in anaesthetized cats.

1. Picrotoxin was perfused through different parts of the cerebral ventricles in cats anaesthetized with chloralose, and applied topically to the upper cervical cord in cats anaesthetized with intraperitoneal pentobarbitone sodium. With both methods, picrotoxin produced effects similar to those produced by tubocurarine; but it was active in weaker concentrations.2. Perfused through the third ventricle, picrotoxin caused shivering resulting in a rise of rectal temperature, increased motor excitability, muscle jerks, tachypnoea, mydriasis, and withdrawal of the nictitating membranes. The effects were due to an action on structures in the walls of the ventral half of the ventricle, because they occurred only on perfusion of tubocurarine through this half and not on its perfusion through the dorsal half of the third ventricle. Noradrenaline perfused through the third ventricle abolished the shivering and the rise in temperature, but did not affect the motor hyperexcitability or the muscle jerks, whereas pentobarbitone sodium similarly perfused abolished these effects as well.3. Perfused through the inferior horn of a lateral ventricle, picrotoxin caused excitation of the hippocampus. This resulted in a rhythmic discharge of high voltage negative spikes in the electrocorticogram taken from the occipital cortices. The spikes developed after-positivity with after-discharges and were interrupted from time to time by bursts of fast activity termed episodes. This abnormal discharge was recorded also from the perfusion cannula which was inserted into the inferior horn and acted as a lead from the surface of the hippocampus.4. Perfused through the anterior horn of a lateral ventricle picrotoxin caused a rhythmic discharge of negative spikes which was recorded from the anterior horn cannula and resulted from excitation of the grey matter in the anterior limbic area which forms part of the medial wall of the horn.5. Applied to the surface of the upper cervical cord, picrotoxin produced scratching movements.

Action Potentials↗

PubMed1981

Distinction between the effects of barbiturates, benzodiazepines and phenytoin on responses to gamma-aminobutyric acid receptor activation and antagonism by bicuculline and picrotoxin.

1 Interactions of depressant and anticonvulsant drugs with the neuronal gamma-aminobutyric acid (GABA) receptor + effector system have been examined on afferent fibres to the rat cuneate nucleus in vitro. Three types of interaction have been measured: (a) potentiation of depolarizing responses to the GABA analogue, muscimol: (b) reduction in the potency of bicuculline as an antagonist of muscimol at the GABA receptor: (c) reduction in the potency of picrotoxin as an antagonist of muscimol acting on the effector mechanism. 2 Phenobarbitone reduced the potency of picrotoxin in doses which did not affect the potency of bicuculline and which caused only a small potentiation of muscimol. Pentobarbitone did not show such selectivity, a reduction in potency of picrotoxin always being accompanied by a reduction in potency of bicuculline and a substantial potentiation of muscimol. 3 Flurazepam and lorazepam both reduced the potency of picrotoxin without affecting that of bicuculline and with very little potentiation of muscimol. Phenytoin had no effect on the potency of picrotoxin whilst potentiating muscimol to the same extent as phenobarbitone. 4 The spectrum of drug activity in reducing the potency of picrotoxin correlates well with the reported anticonvulsant effects of these drugs against kindled amygdaloid seizures. Potentiation of muscimol and reduction of bicuculline potency appear more closely related to hypnotic properties.

Animals↗

PubMed1986

A GABA-activated chloride-conductance not blocked by picrotoxin on spiny lobster neuromuscular preparations.

Conductance increases to gamma-aminobutyric acid (GABA) were recorded in the gm6b and opener muscle of the spiny lobsters, Panulirus interruptus and P. argus. GABA-evoked responses were insensitive to picrotoxin at concentrations as high as 5 X 10(-5) M. Some blockade by picrotoxin was observed at higher concentrations. In normal physiological saline, the reversal potential of the Panulirus GABA-induced response was near the resting potential. The reversal potential was unaffected by reductions in sodium and calcium. Reduction of chloride by 50% resulted in a greater than 10 mV shift in the reversal potential of the GABA-induced response. Muscimol was able to mimic the action of GABA while baclofen was without effect. Bicuculline was a weak blocker. Avermectin B1a irreversibly increased the chloride permeability of the gm6b membrane. This conductance increase was blocked by picrotoxin over a range of concentrations similar to those required for blockade of the GABA-induced response. GABA-induced responses of the gm6b muscle of Homarus americanus were blocked almost completely by picrotoxin 10(-6) M. Sensitivity to picrotoxin is not invariably associated with GABA-activated chloride-mediated conductance increases. It is suggested that alteration in the binding-site for picrotoxin on the GABA-activated chloride-ion channel does not change other functional characteristics of the GABA-induced response.

Action Potentials↗

PubMed1978

Effects of picrotoxin and strychnine on rabbit retinal ganglion cells: changes in centre surround receptive fields.

1. The effects of picrotoxin and strychnine on the centre surround types of ganglion cell (X, Y, sluggish sustained and sluggish transient with on or off centres, and colour coded) were studied in the rabbit retina. 2. Picrotoxin changed the centre surround balance in favour of the centre for Y cells and sluggish transient cells but not for X cells or sluggish sustained cells. 3. Inhibition by a moving radial grating was abolished by picrotoxin for off centre Y cells, but not for on centre Y cells. 4. Picrotoxin abolished the surround response for six on centre sustained cells. These were hybrid cells with conduction velocities and receptive field properties characteristic of more than one of the X, Y and sluggish categories. The surround was not abolished by picrotoxin for any of the cells which fell in the standard X, Y and sluggish categories. 5. Strychnine did not affect the centre surround balance substantially in any of the cells tested. Strychnine did effect the transients: in general strychnine shortened or abolished them, while picrotoxin made them larger.

Action Potentials↗

PubMed1988

Analysis of vertebrate eye movements following intravitreal drug injections. II. Spontaneous nystagmus induced by picrotoxin is mediated subcortically.

1. Eye movements were observed following an injection of picrotoxin, a GABA antagonist, into the vitreous of one eye. A spontaneous nystagmus was observed in cats, rabbits, and turtles, even in total darkness, with slow-phase eye movements in the temporal-to-nasal direction for the injected eye. 2. During visual stimulation by a horizontal drifting pattern, injected eyes moved in the temporal-to-nasal direction, irrespective of stimulus direction. In cats, however, the nystagmus was usually slower when the injected eye viewed nasal-to-temporal motion (opposite to the direction of the spontaneous nystagmus). The spontaneous nystagmus could be halted or even reversed by allowing cats to view motion opposite to the direction of the nystagmus with the uninjected eye alone. The nystagmus could not be overridden in this fashion in rabbits or turtles. 3. The nystagmus induced by picrotoxin could also be modified by vestibular stimulation. When cats were placed on their sides, the spontaneous horizontal nystagmus often decreased and spontaneous vertical nystagmus with upward slow phase movements occurred. During sinusoidal horizontal vestibular stimulation, the horizontal nystagmus due to picrotoxin added to the vestibuloocular reflex as a velocity offset in the temporal-to-nasal direction. 4. Following bilateral ablation of the cat visual cortex, picrotoxin's effect became even more pronounced than before the ablation. Therefore, at least some picrotoxin-sensitive cells can use subcortical pathways, perhaps to the accessory optic nuclei. The visual cortex, which also processes directional information, may be able to compensate for changes in retinal processing induced by picrotoxin in intact animals. 5. This study demonstrates the importance of retinal GABA in the control of eye stability. As GABA is known to be responsible for null direction inhibition of directionally sensitive retinal ganglion cells, these results suggest that the output of these cells may be critical for the normal functioning of central optokinetic pathways, even in the absence of visual cortex.

Animals↗

PubMed1981

Effects of picrotoxin on sensitivity and receptive field properties of ganglion cells in the frog retina.

Action potentials of single ganglion cells were recorded with microelectrodes in excised and opened frog (Rana temporaria L.) eyes before and after picrotoxin application. Area threshold curves were measured both before and after drug application. The drug decreased or abolished the lateral inhibition observed when the cones and green rods were stimulated in the inhibitory receptive fields. In the response pattern interruption often occurs after the first action potentials. Picrotoxin shortened this pause and lengthened the subsequent train of action potentials, i.e., the cell responded with smooth and sustained discharges after picrotoxin application. Picrotoxin also temporarily decreased the sensitivity of the green rod-mediated signals from the excitatory receptive field. Picrotoxin decreased red rod-mediated sensitivity in the completely dark-adapted retina. After an 1-1.5% bleach of the rhodopsin in the dark-adapted eye, the early course of dark-adaptation was similar with and without picrotoxin but after drug application the adaptation curve levelled off at a higher threshold. The organization of the receptive field is discussed in relation to the anatomy, electrophysiology and histochemistry of the cells transmitting the signals from the receptors to the ganglion cells. The role of gamma aminobutyric acid as an inhibitory transmitter in the horizontal and amacrine cell layers is also considered.

Animals↗

PubMed1993

The anticonvulsant effects of propofol, diazepam, and thiopental, against picrotoxin-induced seizure in the rat.

The anticonvulsant effects of propofol administered intravenously against picrotoxin-induced seizure were studied and compared with those of diazepam and thiopental in the rat using picrotoxin-seizure threshold. Comparable doses of the three agents ranging between 1.25-20.0 mg/kg, produced dose-dependent increases in picrotoxin-threshold dose. At the lowest administered dose (1.25 mg/kg), there were no significant differences in picrotoxin-threshold dose among the three agents. Using 2.5 mg/kg dose, propofol and diazepam were equally effective and both were significantly more effective than thiopental in increasing picrotoxin-threshold dose. At higher doses of anticonvulsants (10.0 and 20.0 mg/kg), propofol was significantly more effective than both diazepam and thiopental. These results indicate that propofol is an effective anticonvulsant against picrotoxin-induced seizure, and this effect is significantly greater than diazepam and thiopental at doses producing clear sedative and behavioral effects.

Animals↗

PubMed1990

Modulation of the picrotoxin receptor by fluorinated ethyl, methyl-butyrolactones.

A number of investigators have shown that gamma-butyrolactones bind to the picrotoxin site on the gamma-aminobutyric acid (GABA) receptor. We examined the effects of three fluorinated gamma-butyrolactone derivatives on GABA currents and synaptic currents in cultured hippocampal neurons. alpha-(2,2,2-trifluoroethyl)-alpha-methyl-gamma-butyrolactone was a partial picrotoxin agonist, meaning that like picrotoxin, it blocked GABA currents, but not completely. This action is in marked contrast to that of its parent compound, alpha-ethyl-alpha-methyl-gamma-butyrolactone, which is a mixed inverse agonist/antagonist, enhancing GABA currents at low GABA concentration (less than or equal to 1 microM) and antagonizing picrotoxin block of GABA currents at higher GABA concentrations (approximately 30 microM). The properties of two difluorinated derivatives were found to be very different from the trifluorinated compound. Both alpha-(1,1-difluoroethyl)-alpha-methyl-gamma-butyrolactone and alpha-(1,1-difluoroethyl)-alpha-methyl-gamma-thiobutyrolactone+ ++ dramatically increased the current produced by low concentrations of GABA. The former had less marked inverse agonist effects at higher GABA concentrations but behaved instead like a picrotoxin antagonist. In addition, alpha-(1,1-difluoroethyl)-alpha-methyl-gamma-butyrolactone reduced both excitatory and inhibitory synaptic currents suggesting a separate effect on presynaptic transmitter release through an unknown mechanism. These experiments support the hypothesis that gamma-butyrolactones can have a variety of effects at the picrotoxin receptor and indicate that specific properties of these compounds can be altered drastically by fluorination.

4-Butyrolactone↗

PubMed1995

Picrotoxin is a CYP1A1 inducer in rainbow trout hepatocytes.

Picrotoxin is a CYP2B inducer in mammals (1). However, in primary cultures of rainbow trout hepatocytes we showed CYP1A1 gene expression to be strongly induced as characterized by 7-ethoxyresorufin-O-deethylase activity, immunoblots of CYP1A1 protein, and Northern blots of CYP1A1 mRNA. Induction of CYP1A1 in these cells appeared to be via the aromatic hydrocarbon (Ah) receptor as indicated by increased levels of Ah receptor in the nuclear extracts of picrotoxin-treated cells. Picrotoxin induction of CYP1A1 was blocked by actinomycin D. Superinduction of CYP1A1 mRNA occurred in cells treated with cycloheximide. Co-incubation of hepatocytes with picrotoxin and a saturating concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in synergistic increases in CYP1A1 gene expression. These results suggest that picrotoxin induction of CYP1A1 is regulated at the level of transcription and may involve an alternative mechanism(s) to that of TCDD.

Animals↗

PubMed1992

Dopamine and endogenous opioid regulation of picrotoxin-induced locomotion in the ventral pallidum after dopamine depletion in the nucleus accumbens.

Microinjection of picrotoxin or the mu-opioid agonist, Tyr-D-Ala-Gly-NmePhe-Gly-OH (DAMGO), into the ventral pallidum (VP) produces an increase in locomotor activity that is antagonized by dopamine receptor blockade. To investigate the regulation of VP-induced locomotion by the dopaminergic innervation of the nucleus accumbens (NA) and the role of opioid receptors in this regulation, dopamine innervation of the NA was bilaterally lesioned with 6-hydroxydopamine (6-OHDA). The lesions resulted in an 89-97% depletion of tissue dopamine levels in the nucleus accumbens compared with sham-lesioned rats. Dopamine depletion in the NA failed to significantly antagonize picrotoxin or DAMGO injected into the VP. However, the dopamine receptor antagonist, haloperidol (0.1 mg/kg, IP), blocked the picrotoxin-initiated increase in horizontal photocell counts in both sham- and 6-OHDA-lesioned rats. The opioid receptor antagonist, naloxone (1.0 mg/kg, SC), also blocked the picrotoxin-induced locomotion in 6-OHDA-lesioned rats but did not block locomotion in the sham-lesioned rats. At a higher dose (3.0 mg/kg, SC), naloxone blocked picrotoxin-induced locomotion in both sham- and 6-OHDA-lesioned rats. These results indicate that although dopamine depletion in the NA does not affect the permissive role of dopamine transmission on locomotion elicited from the VP, it results in an increased sensitivity to enkephalinergic transmission.

Animals↗

PubMed1999

Picrotoxin in the medial prefrontal cortex impairs sensorimotor gating in rats: reversal by haloperidol.

RATIONALE: Neuropathological data indicate a GABAergic dysfunction in the prefrontal cortex and hippocampus of schizophrenics. On this basis, the construct validity of an animal model of schizophrenia was tested. OBJECTIVE: This study assessed prepulse inhibition (PPI) of startle in rats after injections of the GABA antagonist picrotoxin into the prefrontal cortex and the ventral hippocampus. It was also tested if reductions in PPI are reversed by the dopamine antagonist haloperidol. PPI is a measure of sensorimotor gating and is impaired in schizophrenia patients. The hypothesis underlying this study was that blockade of prefrontocortical and hippocampal GABA receptors disrupts PPI in a dopamine-dependent way. This hypothesis was based on neuropathological data from schizophrenics indicating a loss of GABAergic neurons in the prefrontal cortex and hippocampus and on the observation that PPI is reduced in schizophrenics. METHODS: Picrotoxin (0, 5, 10 ng/0.5 microl) was infused through chronically indwelling cannulae into the medial prefrontal cortex (mPFC), into the lateral prefrontal cortex and into the ventral hippocampus. The effect on PPI was measured directly after picrotoxin infusion. The neuroleptic compound haloperidol (0.1 mg/kg) was administered intraperitoneally 30 min before testing. RESULTS: Picrotoxin in the mPFC dose-dependently reduced PPI and this effect was antagonized by systemic pretreatment with the dopamine antagonist haloperidol. No significant effects on PPI were observed after picrotoxin infusions into the lateral prefrontal cortex or into the ventral hippocampus. CONCLUSIONS: These findings indicate that acute blockade of GABA receptors in the mPFC impairs sensorimotor gating in a dopamine-dependent manner. Since PPI in rats has been shown to possess face, predictive, and construct validity as an animal model for some psychotic symptoms, we discuss the potential relevance of our findings for the pathophysiology of schizophrenia.

Animals↗

PubMed2005

Role of cAMP-dependent protein kinase on acute picrotoxin-induced seizures.

cAMP-dependent protein kinase (PKA) is a major modulator of synaptic transmission likely to be involved in molecular and cellular events leading to epileptogenesis, but little is known about how it affects the onset of acute epileptic seizures. In this study, we determined PKA enzymatic activity in the rat hippocampus during picrotoxin-induced seizures, using H-9 dihydrochloride, a PKA inhibitor, to investigate the in vivo effects of this enzyme on seizures induced by picrotoxin microdialysis in the rat hippocampus. No significant modifications were found in PKA activity during seizures as compared to control rats, but H-9 dihydrochloride microperfusion (100 microM) prevented picrotoxin seizures in 50% of the animals and significantly reduced the mean number of seizures and mean seizure duration. These results suggest that acute picrotoxin-induced seizures occur without an increase in hippocampal PKA activity, but reduced PKA-mediated phosphorylation protects against picrotoxin seizures, probably by increasing the inhibitory potential of GABA(A) receptors. The possibility of other targets for H-9 dihydrochloride, such as PKC, PKG or CAMKII, however, cannot be ruled out.

Animals↗

PubMed1976

Increase in striatal acetylcholine by picrotoxin in the rat: evidence for a gabergic-dopaminergic-cholinergic link.

Picrotoxin, 2 mg/kg i.p., a GABA receptor blocking agent, increased rat striatal acetylcholine content by approximately 70% without altering the levels of this amine in the cerebral hemispheres, mesencephalon, diencephalon, hippocampus and cerebellum. Striatal choline levels were concomitantly decreased by about 25%. This dose of picrotoxin also increased striatal homovanillic acid levels by about 30%, an effect which was not antagonized by pretreatment with the dopamine receptor stimulating agent, piribedil. Picrotoxin did not affect striatal choline-O-acetyltransferase or cholinesterase activity after in vitro incubation. The action of picrotoxin on striatal acetylcholine levels was partially antagonized by pimozide and completely blocked by alpha-methyl-para-tyrosine pretreatment while the intraventricular injection of 6-hydroxydopamine was without effect. Convulsions were not prevented by any of these treatments. The results are interpreted as follows: picrotoxin released dopamine through disinhibition of the dopaminergic neurons as a result of blockade of gabergic receptors. The increased dopaminergic activity inhibited cholinergic neurons and lead to an increase in acetylcholine content. The data thus provide evidence for a possible gabergic (inhibitory)--dopaminergic (inhibitory)-cholinergic link terminating in the striatum.

Acetylcholine↗

PubMed1987

Glutamate and picrotoxin injections into the preoptic basal forebrain initiate locomotion in the anesthetized rat.

This study determined the locomotor effects of glutamate and picrotoxin injections and electrical stimulation in the preoptic basal forebrain. Male rats, anesthetized with Nembutal, were held in a stereotaxic apparatus such that stepping rotated a wheel. Cathodal stimulation (0.5-ms pulses, 50-Hz frequency, 10-s train, less than 100 microA) was applied through a 30-gauge stainless-steel, insulated cannula to find locomotor sites. Glutamate (20 mM or 2 M) or picrotoxin (100 or 200 ng) were injected in volumes of 0.2 or 0.1 microliter of saline at a rate of 1 microliter/5 min. Electrical stimulation elicited locomotion (principally hindlimbs) in 32 sites which included the lateral and medial preoptic areas and the bed nucleus of the stria terminalis (BST). Stimulation in 23 sites, most in the BST and septal area, failed to produce locomotion. Stepping was elicited by glutamate and electrical stimulation in 15 sites. Glutamate was ineffective at 21 sites, at 6 of these sites electrical stimulation was effective. Longer bouts of locomotion were produced by 20 nM glutamate. Picrotoxin produced more intense and prolonged locomotion than glutamate. It was effective in 15 sites, at 12 of which electrical stimulation was also effective. At some ventral sites, picrotoxin-elicited stepping was continuous, at others it appeared in bursts of 5-20 s duration. At dorsal sites, the locomotor bursts were punctuated by episodes of pelvic flexion. Picrotoxin was ineffective at 12 sites, 7 of which were effective with electrical stimulation. These results indicate that activity of neurons in the preoptic basal forebrain can initiate locomotion.

Anesthesia↗

PubMed1989

Steroid hormone effects on picrotoxin-induced seizures in female and male rats.

Picrotoxin (1 mg/kg, i.p.), evoked a single generalized seizure in 75% of ovariectomized rats. Pretreatment of matched pairs with silastic implants containing 100% estradiol had an anticonvulsant effect; it protected all rats against such seizures. Implants containing 10% estradiol in cholesterol were less effective in protecting against picrotoxin-induced seizures. With 2 mg/kg picrotoxin, 85% of the seizure-affected ovariectomized controls had multiple seizures. The incidence of seizures and the ratio of single to multiple seizures induced by the higher dose of picrotoxin were unaffected by estradiol silastic implants, intraperitoneal injections of progesterone (0.5 mg, 4-5 h before convulsant) or the combination of both hormones. At the 2 mg/kg dose, 8/8 intact males had no seizures while all paired ovariectomized females had seizures. By contrast, the incidence of seizures in pairs of gonadectomized males and females did not differ. Testosterone treatment improved the ratio of single to multiple seizures in males but not in females. Males had statistically fewer multiple seizures than did females after testosterone treatment. The distribution of latencies to a single seizure is statistically different from the distribution of latencies to the first of multiple seizures irrespective of dose, sex and hormone treatment. This suggests that the population of rats responding with a single seizure at the higher dose of picrotoxin have a higher threshold for acquiring multiple seizures and that testosterone predisposes males but not females to this population.

Animals↗

PubMed1989

Similarities between the effects of lindane (gamma-HCH) and picrotoxin on ligand-gated chloride channels in crayfish muscle membrane.

Effects of lindane (gamma-HCH) and picrotoxin have been tested on excised outside-out patches of crayfish stomach muscle membrane. The pulsed application of 10(-3) M gamma-aminobutyric acid (GABA) elicited an inward CL- current of several 100 pA, which could be reversibly reduced by the simultaneous application of lindane or picrotoxin. The rise time and desensitization time constant of the GABA response did not seem to be affected. The apparent KI was 5 x 10(-6) M for lindane and 15 x 10(-6) M for picrotoxin. Also Cl- currents induced by glutamate or acetylcholine could be reversibly reduced by lindane or picrotoxin. The evaluation of single Cl- channel openings which were elicited by the simultaneous application of glutamate and lindane showed no effect of lindane on the unitary conductance and on the mean open time of these channels. A mechanism for the antagonistic action of lindane and picrotoxin is discussed.

Animals↗

PubMed1984

Inhibition of seizures induced by picrotoxin and electroshock by cholecystokinin octapeptides and their fragments in rats after intracerebroventricular administration.

The anticonvulsive activity of cholecystokinin octapeptide sulphate ester (CCK-8-SE), non-sulphated cholecystokinin octapeptide (CCK-8-NS) and three different N- and C-terminal fragments were investigated against seizures induced by picrotoxin and electroshock in rats after intracerebroventricular administration. Doses of 0.8 and 80 pmol of CCK-8-SE and CCK-8-NS significantly enhanced the latency of seizures induced by picrotoxin and shortened the duration of the clonic phase of the seizures induced by electroshock. Only CCK-8-SE shortened the recovery time and only 0.8 pmol of CCK-8-SE could shorten the duration of the tonic phase of convulsions induced by electroshock. Doses of the octapeptides of 8000 pmol were ineffective, with the exception of CCK-8-NS in the picrotoxin test. Of the fragments tested, the C-terminal tetrapeptide, CCK-5-8, enhanced the latency of seizures induced by picrotoxin in a dose of 0.8 pmol, and had a dose-dependent biphasic effect on the duration of the clonic phase of seizures induced by electroshock. Intracerebroventricular administration of diazepam enhanced only the latency of tremor and clonic seizures induced with picrotoxin in a dose of 40 nmol. Twelve nmole of diazepam shortened the clonic phase of convulsions induced by electroshock. The peptides tested were much more active than diazepam, and their effective doses were comparable to the amounts of cholecystokinin octapeptide found in brain structures.

Animals↗

PubMed1984

Do the reductions in social interaction produced by picrotoxin and pentylenetetrazole indicate anxiogenic actions?

The effects of picrotoxin (2 and 4 mg/kg) and of pentylenetetrazole (PTZ 5, 10 and 20 mg/kg) were examined in a social-interaction test of anxiety. Picrotoxin (2 mg/kg) caused a significant reduction in active social interaction, without a concomitant reduction in motor activity, indicating an anxiogenic action. Picrotoxin (4 mg/kg) and pentylenetrazole (20 mg/kg) reduced social interaction by more than 75% and motor activity by 40%. Although it is likely that the reduction in motor activity is secondary to the very low levels of social interaction, an unambiguous interpretation of an anxiogenic effect is not possible. Increased concentrations of corticosterone in plasma following administration of picrotoxin were consistent with the drug being anxiogenic. Chlordiazepoxide (5 mg/kg) significantly reversed the reductions in social interaction and locomotor activity following injection of picrotoxin (4 mg/kg) and PTZ (20 mg/kg).

Animals↗