Geochemistry of mineral licks at Loskop Dam Nature Reserve, Mpumalanga, South Africa.

Although numerous hypotheses have been proposed to explain geophagy, the primary driver of this behaviour remains elusive. Supplementation of scarce nutrients is one commonly cited explanation. We examined the element concentration of three licks relative to adjacent topsoils to infer the possible reasons for geophagy at Loskop Dam Nature Reserve. Lick samples had greater concentrations of B, Co, Zn, Se, Mo and Mn (Loskop Main Lick); Cu (Klopperskloof Lick); and Na (Klopperskloof Lick and Rhenosterhoek Lick) than those of adjacent topsoil. We suggest that supplementation with all or some of these nutrients is a likely driver of geophagy in this fenced reserve, with different licks providing herbivores with different suites of nutrients.

Theta driving both inhibits and potentiates the effects of nicotine on dentate gyrus responses.

The medial septal area of conscious rats was stimulated through previously implanted electrodes at a frequency of 7.7 Hz for 20 min each day for 7 days to evoke rhythmic slow activity in CA1 at a similar frequency to spontaneous theta. Two weeks later in the anaesthetized rats the effects of a single subcutaneous injection of nicotine (0.4 mg/kg) on fEPSPs, evoked in the dentate gyrus by separate stimulation of the MPP and LPP, were studied and compared with those obtained in controls. Nicotine increased the firing of locus coeruleus neurons and the slope of the fEPSPs evoked by LPP stimulation, but not by MPP stimulation. Prior theta driving considerably increased the effect of nicotine on the responses evoked by stimulation of the MPP and abolished the nicotine-induced potentiation of the responses evoked by stimulation of the LPP. The results are attributed to theta driving increasing the amount of noradrenaline released by nicotine and to noradrenaline producing a beta-adrenoceptor long-lasting potentiation at the medial perforant path synapse and a long-lasting depression at the lateral perforant path synapse.

Theta driving both inhibits and potentiates the effects of nicotine on dentate gyrus responses.

The medial septal area of conscious rats was stimulated through previously implanted electrodes at a frequency of 7.7 Hz for 20 min each day for 7 days to evoke rhythmic slow activity in CA1 at a similar frequency to spontaneous theta. Two weeks later in the anaesthetized rats the effects of a single subcutaneous injection of nicotine (0.4 mg x kg(-1)) on fEPSPs, evoked in the dentate gyrus by separate stimulation of the MPP and LPP, were studied and compared with those obtained in controls. Nicotine increased the firing of locus coeruleus neurones and the slope of the fEPSPs evoked by LPP stimulation, but not by MPP stimulation. Prior theta driving considerably increased the effect of nicotine on the responses evoked by stimulation of the MPP and abolished the nicotine-induced potentiation of the responses evoked by stimulation of the LPP. The results are attributed to theta driving increasing the amount of noradrenaline released by nicotine and to noradrenaline producing a beta-adrenoceptor long-lasting potentiation at the medial perforant path synapse and a long-lasting depression at the lateral perforant path synapse.

Biphasic effects of atropine on sensory-evoked hippocampal rhythmical slow activity in urethane-anaesthetized rats.

This study investigated the response of hippocampal RSA, recorded from electrodes in CA1 and the contralateral dentate gyrus of urethane-anaesthetized rats, to atropine sulphate administered at 15 min intervals in a cumulative dose-response schedule (1, 3, 10, 50 and 50 mg x kg(-1) i.p.). The power of CA1 and dentate gyrus RSA in the 3-7 Hz band was increased after administering the first 3 doses of atropine (1, 3 and 10 mg x kg(-1) cumulatively) in rats held in the stereotaxic frame or removed from the frame and given electrical sensory stimulation to the base of the tail. This increase in RSA was dependent on sensory input, since it was not seen in animals outside the frame unless sensory stimulation was given, and it was abolished by increasing the dose of atropine (an additional 50 and 50 mg x kg(-1) cumulatively). Methylatropine (6 mg x kg(-1) i.p.) did not increase RSA power. The biphasic effect of atropine on sensory-evoked hippocampal RSA activity may be explained by differential effects at pre- and post-synaptic sites e.g. in the septo-hippocampal system or on pathways processing sensory information.

Importance of forebrain cholinergic and GABAergic systems to the age-related deficits in water maze performance of rats.

The present study investigated the performance of rats at 3-4 months and 21 months of age in the Morris water maze and correlated age-related cognitive deficits with changes in both cholinergic and GABAergic systems in the frontal cortex. The older rats were divided into two groups, unimpaired old and impaired old according to their ability to find a hidden submerged platform in the water maze, for electrophysiological, neurochemical, and morphological studies. The firing rate of frontal cortical neurones was recorded from the motor area of the frontal cortex under urethane anaesthesia and was found to be significantly slower in the two aged groups of rats compared to the young rats, but there were no differences between the two aged groups. The sensitivity of frontal cortex neurones of the impaired and unimpaired old age groups to ACh and to carbachol was significantly lower than that of the young group, but there were no differences between the two old age groups. In contrast, sensitivity of frontal cortex neurones to bicuculline was significantly higher in the aged rats compared with the young rats and was significantly greater in the impaired old rats than in the unimpaired old rats. The sensitivity of cortical neurones to glutamate was unaffected by age. There were also significant correlations between the percentages of cortical neurones responding to ACh and bicuculline and different parameters of water maze acquisition during days 7-8, but not during days 2-3, when spatial learning had not begun, and days 13-14, when spatial learning was complete. Biochemical and morphological analyses did not show any significant differences in ChAT activity and AChE-positive fibre density in the frontoparietal cortices of the three groups of rats. The results demonstrate that the learning deficit observed in old age rats cannot be adequately explained solely by a reduction in cholinergic receptor sensitivity and that an age-related increase in GABAergic tone may be a more important determinant of cognitive impairment.

The effects of parasympathetic blocking agents on bladder electromyograms and function in conscious and anaesthetized cats.

Voiding induced in conscious cats by infusion of sterile saline into the bladder via a chronically implanted bladder catheter was stable over many months. Artefact-free recordings of electrical activity obtained from the bladder neck and dome of these preparations during bladder filling and voiding showed characteristic voiding electromyograms but did not permit a functional differentiation. Both voiding and the associated electromyogram were abolished by the ganglion blocking agent, pentolinium. Hyoscine or methyl atropine did not affect the electromyogram but impaired the ability of cats to empty their bladders completely. In anaesthetized cats, ganglion blocking agents prevented a rise in bladder pressure during sacral ventral root stimulation but a hyoscine-sensitive bladder contraction was seen following the period of stimulation. Further stimulation during this post-stimulus rise in intravesical pressure revealed a hyoscine-sensitive stimulus-bound relaxation. Sacral ventral root stimulation relaxed the bladder neck/proximal urethra particularly in the presence of sympathetic tone.

Effects of desipramine on cardiovascular responses of rats to stimulation of the baroreceptor reflex and of central adrenoceptors.

Phenylephrine (0.4-2.0 micrograms 300 g-1), injected intravenously, evoked similar dose-dependent increases in blood pressure in untreated rats and in rats treated with desipramine (10 mg kg-1 day-1 for 4 weeks). The (dose-dependent) reflex fall in heart rate to the blood pressure responses were smaller in the rats treated with desipramine. Treatment with desipramine did not affect the bradycardia evoked by intrahypothalamic injection of phenylephrine (10 micrograms). After treatment with desipramine, the hypotension evoked by intrahypothalamic injection of isoprenaline (10 micrograms) was enhanced whereas the evoked tachycardia was diminished.

Classification of opioid and 5-hydroxytryptamine receptors by means of discriminative drug effects.

Behavioural studies can help to validate, modify and refine schemes for classifying receptors that are developed from electrophysiological and biochemical experiments. Drug discrimination constitutes one family of behavioural techniques that is being extensively used for studying subtypes of receptors, mainly because the methods often have remarkably high pharmacological specificity but can be applied to agents from a diverse range of classes. This article reviews briefly studies on agents acting through opioid and 5-hydroxytryptamine systems, where the results of the behavioural studies are very largely consistent with findings from other approaches. Many drugs used in such work have limited selectivity for putative subtypes of receptor, but little is known about how such compound pharmacological stimuli are processed in drug discrimination experiments. The characteristics of the discriminative stimuli produced by a mixture of drugs are discussed with respect to implications for effects of single drugs with multiple actions. Based on these initial experiments on discrimination of a mixture of nicotine and midazolam, it appears that the components of a compound pharmacological stimulus may be perceived and processed independently.

Effect of desipramine, phenoxybenzamine and yohimbine on beta-adrenoceptors and cyclic AMP production in the rat brain.

In rat brain, the number of beta-adrenoceptors and activity of noradrenaline-dependent adenylate cyclase were examined after treatment with desipramine (7.5 mg kg-1 day-1) for three days alone or in combination with the alpha 2-adrenoceptor antagonist, yohimbine (2 mg kg-1 12 hr-1), or with phenoxybenzamine (7.5 mg kg-1 day-1), which is a more potent inhibitor of alpha 1 than alpha 2-adrenoceptors. The only treatment which significantly decreased the specific binding of the beta-adrenoceptor antagonist, [3H]dihydroalprenolol was the combination of desipramine with yohimbine. Desipramine alone and desipramine with yohimbine also significantly reduced the formation of cyclic AMP in response to incubation with noradrenaline, the response to the drug combination being accounted for by addition of the individual effects of the drugs. The results showed that decreases in the activity of noradrenaline-dependent adenylate cyclase could become apparent before decreases in beta-adrenoceptor numbers. Whether these rapid changes in noradrenaline-dependent adenylate cyclase or in numbers of beta-adrenoceptors which are produced by combination of desipramine with an alpha 2-adrenoceptor antagonist, are of therapeutic value remains to be elucidated.

Changes in paired-pulse facilitation correlate with induction of long-term potentiation in area CA1 of rat hippocampal slices.

The phenomenon of long-term potentiation is widely used as an experimental model of memory. An approach that has been used to study its underlying mechanisms is to analyse its interaction with presynaptic paired-pulse facilitation. Several studies found no evidence for an interaction in the CA1 hippocampal area, whereas other data, for example from quantal analysis, suggested that presynaptic mechanisms contribute to the maintenance of long-term potentiation. In the present study, initial slopes of field potentials in area CA1 were measured in rat hippocampal slices. "Conventional" long-term potentiation was induced by high-frequency (100 Hz) afferent tetanization of the testing input. "Associative" long-term potentiation was induced by combining lower frequency (40 Hz) tetanization of a testing input with high-frequency tetanization of a second input. The paired-pulse facilitation ratio decreased in the majority of experiments in which long-term potentiation was induced conventionally, but it decreased, increased or did not change after inducing associative potentiation. Decreases in the paired-pulse facilitation correlated inversely with the initial (pre-tetanic) facilitation ratio. A more detailed regression analysis suggests that this correlation results from two other correlations: (i) that between changes in paired-pulse facilitation and the magnitude of long-term potentiation, and (ii) that between initial paired-pulse facilitation and the magnitude of long-term potentiation. The first correlation prevailed during the initial 10 min following tetanization, while the second prevailed 40-60 min later. A post-tetanic decrease in paired-pulse facilitation is evidence for an involvement of presynaptic mechanisms in the maintenance of long-term potentiation. The lack of significant changes in some studies could be due to the inclusion in the analyses of experiments with long-term potentiation of small magnitude, in which changes in paired-pulse facilitation ratios would have been inconsistent. The present study suggests that the early (10-20 min) and late (40-50 min) phases of long-term potentiation were mediated by different mechanisms, with a mixture of these mechanisms during the intermediate period. On the basis of the present and previous studies, the following scheme of involvement of several mechanisms in long-term potentiation maintenance is proposed. The early phase includes two major mechanisms: an increase in the probability of transmitter release, leading to an apparent increase in the number of effective release sites, and an increase in efficacy of one transmitter quantum, probably due to an increased number of postsynaptic receptors. The later phase of long-term potentiation is attributed to an increase in the number of transmitter zones, presumably due to structural modifications.

Effects of noradrenaline and carbachol on temperature regulation of cold-stressed and cold-acclimated rats.

1 Noradrenaline (20 micrograms) and carbachol (1 microgram) injected into the anterior hypothalamus of rats at an ambient temperature of 23 degrees C evoked significant falls in core temperature and increases in tail temperature. 2 When rats were cold-stressed (4 degrees C for 90 min) or cold-acclimated (4 degrees C for 4 weeks) and the above amine injections repeated, only carbachol evoked significant falls in core temperature and neither amine increased tail temperature. 3 Central injections of noradrenaline and carbachol also evoked increases in plasma glucose concentrations but not plasma non-esterified fatty acid (NEFA) concentrations in control, acutely cold-stressed and cold-acclimated rats. 4 Although concentrations of plasma glucose and blood lactate of rats were unaffected by cold exposure to 4 degrees C for 1 to 28 days, glucose oxidation rate of both cold-stressed and cold-acclimated rats was significantly greater than in rats at 23 degrees C. Concentrations of plasma NEFA were increased after 1 to 28 days of cold exposure.

Effects of noradrenaline and carbachol on temperature regulation of rats.

1 Noradrenaline (0.2 to 20 micrograms) and carbachol (0.1 to 1 microgram) injected into the preoptic/anterior hypothalamic area, evoked dose-dependent falls in core temperature at all sites tested, followed in most experiments by delayed increases that were not dose-related. Muscarine (0.1 to 10 microgram) produced effects similar to those evoked by carbachol. 2 These falls in core temperature were associated with increases in tail temperature, locomotor activity and CO2 elimination (a measure of metabolic rate). 3 The temperature responses to noradrenaline (10 microgram) and to carbachol (1 microgram) were antagonized by intrahypothalamic injections of phentolamine (10 microgram) and atropine (1 microgram), respectively. 4 Analysis of the temperature responses and their respective latencies indicates that carbachol-induced hypothermia was mediated by cholinoceptors in the anterior hypothalamus, whereas hypothermia after noradrenaline was mediated by adrenoceptors throughout the preoptic/anterior hypothalamic area. 5 Vasodilatation of the tail blood vessels contributed significantly to the hypothermia evoked by carbachol, and to that evoked by injections of noradrenaline into the anterior hypothalamus. 6 Hypothermia induced by noradrenaline injection into the preoptic area, was mediated by effector mechanisms additional to non-evaporative heat loss.

Effects of catecholamines infused into the brain of young chickens.

1. (-)-Noradrenaline, (-)-alpha-methylnoradrenaline and (-)-isoprenaline were infused into various brain regions of 12-21 day chicks. When infused into the hypothalamic area, but not the cerebral hemisphere or posterior mesencephalon, these amines produced behavioural sleep, lowered temperature and blood pressure and reduced oxygen consumption; electrocortical sleep activity usually ensued but this was not marked and frequently dissociation between electrocortical activity and behaviour occurred. After monoamine oxidase inhibition, which prolonged the action of noradrenaline, dopamine had similar effects.2. The effects of the catecholamines were prevented or substantially reduced by pretreatment with phenoxybenzamine given intravenously or into the hypothalamus but not by intravenous injection of propranolol. However, intrahypothalamic infusion of propranolol prevented the temperature, but not the behavioural effects of noradrenaline. The implications of this are discussed.3. That the effects were similar but more intense, apart from electrocortical changes, and of longer duration than those seen after intravenous injection of catecholamines suggests that in young chicks these amines penetrate from the blood into the brain and elicit their effects through a localized region, presumably the hypothalamus.

Actions of dexamphetamine and amphetamine-like amines in chickens with brain transections.

1. A method for preparing the encéphale isolé preparation in young fowls is described. Certain important differences were found between electrocortical activity of chicken and mammalian encéphale isolé preparations. Electrocortical effects of excitant sympathomimetic amines and their antagonism were readily quantified because of stable electrocortical activity of the chick encéphale isolé preparation.2. Amphetamine-like excitant amines ((+)- and (-)-amphetamine, alpha-methyltryptamine, tryptamine, beta-phenethylamine, cyclopentamine, beta-tetrahydronaphthylamine and tuaminoheptane) evoked electrocortical desynchronization in chick encéphale isolé preparations, confirming the central origin of these effects. Behavioural changes were also observed.3. The electrocortical response to these amines was antagonized by methysergide, a selective tryptamine antagonist and by a catecholamine, alpha-methylnoradrenaline. Behavioural changes were also antagonized.4. Electrocortical desynchronization to dexamphetamine was prevented by an anterior transection of the brain which separated the telencephalon from the diencephalon. More posterior transections reduced the duration of the electrocortical response to dexamphetamine; intensity of response was either increased or decreased.

Effects of spiperone on self-stimulation and other activities of the Mongolian gerbil.

1 Self-stimulation to lever pressing and capacitance probe touching was obtained in Mongolian gerbils (Meriones unguiculatus) from electrode placements within the medial forebrain bundle. 2 Lever pressing was more sensitive to the decremental effects of a central depressant, pentobarbitone, than capacitance probe touching, suggesting its greater responsiveness to disturbances of motor function. 3 Spiperone (0.005 to 0.05 mg/kg) attenuated capacitance probe touching and lever pressing equally, a finding explained by action on either reward pathways or on the ability to initiate responding. 4 This same dose range of spiperone (0.005 to 0.05 mg/kg) attenuated locomotor activity, whether spontaneous or evoked by non-contingent electrical stimulation, and produced catalepsy. 5 The spiperone-induced attentuation of self-stimulation was not necessarily a result of its action on dopaminergic reward pathways since the effects could equally well be explained by a failure to initiate responding.

Some effects of intravenous prostaglandin E, and endotoxin in young chickens.

1 The effects of intravenous prostaglandin E1 and endotoxin were studied in young chickens (11-17 days old). 2 At a thermoneutral ambient temperature (31 degrees C), intravenous prostaglandin E1, produced behavioural and electrocortical sleep, increased oxygen consumption and, after an initial fall, elevated body temperature. Below thermoneutrality (16 degrees C), the initial hypothermic effect was more marked and oxygen consumption was lowered. 3 The soporific actions of prostaglandin E1 were sufficient to counteract dexamphetamine-induced behavioural and electrocortical arousal and vocalization. 4 Intravenous injection of the O-somatic antigen of Shigella dysenteriae evoked, after a latent period, long lasting hyperthermia. This indicates that in young chicks the blood brain barrier is probably permeable to endotoxins.

Some effects of prostaglandins E1 and E2 and of endotoxin injected into the hypothalamus of young chicks: dissociation between endotoxin fever and the effects of prostaglandins.

Prostaglandins E1 and E2 elevated body temperature of young chicks when injected into the hypothalamus at thermoneutrality (31 degrees C). In contrast, they lowered body temperature when so injected below thermoneutrality (16degreesC): the relation of the fall in body temperature to increased heat loss and decreased heat production was examined. 2 The above effects below thermoneutrality were potentiated by pretreatment with inhibitors of prostaglandin synthetase and possible reasons for this potentation are given. 3 The O-somatic antigen of Shigella dysenteriae consistently evoked hyperthermia when injected into the hypothalamus, irrespective of whether the chicks were within or below thermoneutrality. 4 Pretreatment with prostaglandin synthetase inhibitors failed to prevent the onset of endotoxin fever; however, duration of the fever, induced by intrahypothalamic injection of the O-somatic antigen of Shigella dysenteriae was reduced. 5 The intrahypothalamic injection, belwo thermoneutrality of prostaglandins E1, E2, noradrenaline, 5-hydroxytryptamine or carbachol reversed endotoxin fever, inducing even substantial falls in body temperature. 6 While the results cast some doubts on the role of prostaglandins of the E series as mediators of endotoxin fever in chicks, they cannot be eliminated as mediators until the significance of the reduction in duration of the pyrexic response by indomethacin and 5,8,11,14-eicosatetraynoic acid, and the degree of synthesis inhibition attained, are known.

The effect of chronic ritanserin and clorgyline administration on 5-HT2 receptor linked inositol phospholipid hydrolysis.

We have previously shown that chronic administration of the 5-hydroxytryptamine (5-HT) receptor antagonist, ritanserin (10 mg/kg/day) or the monoamine oxidase type A inhibitor (MAOI), clorgyline (2 mg/kg/day), results in a reduction in 5-HT2 receptor number in rat cerebral cortex. This study investigates the effects of acute and chronic ritanserin administration, on 5-HT2 receptor linked inositol phospholipid hydrolysis in rat cortical slices and compares it with the effect of a chronic clorgyline regimen. [3H]Myo-inositol (50 microCi) was used to label inositol phospholipids. Their subsequent hydrolysis in the presence or absence of 5-HT was determined by the accumulation of [3H]myoinositol monophosphate ([3H]InsP). Addition of 5 nM ritanserin to slices had no effect on basal or 5-HT stimulated [3H]InsP accumulation whereas 100 nM ritanserin blocked the stimulated response by 65%. Acutely, ritanserin (15 mg/kg i.p.) completely blocked 5-HT stimulated [3H]InsP accumulation. Chronic ritanserin or clorgyline treatment had no effect on basal levels of [3H]InsP accumulation compared to controls (mean value 3125 +/- 298 dpm/mg protein). Ritanserin increased 5-HT stimulated [3H]InsP accumulation at 1 microM, 100 microM and 1 mM 5-HT and this effect was significant at 100 microM 5-HT. Clorgyline had no significant or consistent effect on 5-HT stimulated [3H]InsP accumulation at 1 microM, 100 microM and 1 mM 5-HT. Thus the effects of both chronic clorgyline and ritanserin administration on 5-HT2 linked inositol phospholipid hydrolysis do not correlate with their effects on 5-HT2 receptor number (Bmax). The situation is further complicated since ritanserin significantly increases phosphatidylinositol (PtdIns), phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) labelling whereas clorgyline significantly increases PtdIns and PtdIns4P labelling. The implications of this are discussed.

Chronic treatments with cholinoceptor drugs influence spatial learning in rats.

Nicotine, scopolamine, oxotremorine, diisopropyl-fluorophosphate (DFP) and tetrahydroaminoacridine (THA) were administered chronically to different groups of rats in doses reported to alter central muscarinic and/or nicotinic receptor numbers. Beginning 24 h after final drug injection, the groups were compared to a vehicle control group on acquisition of a hidden platform position in the Morris water maze over 20 trials with a 30-min inter-trial interval. Chronic treatment with either nicotine or scopolamine significantly improved the rate of learning, but oxotremorine and DFP retarded learning and THA had no effect on learning. The chronic drug effects on behaviour were consistent with known effects of the injected drugs on muscarinic and nicotinic binding in the forebrain and on the sensitivity of frontal cortex neurones to iontophoretically applied cholinoceptor agonists. However, alternative explanations for the observed changes cannot be ruled out, since the drugs used are known to have a wide range of effects on other neurotransmitters.

Enhancement of latent inhibition by two 5-HT2A receptor antagonists only when given at both pre-exposure and conditioning.

RATIONALE: Clozapine-like atypical antipsychotic drugs, such as olanzapine, risperidone and sertindole, bind most strongly to 5-HT(2A) receptors, which may contribute to their antipsychotic effects. Antipsychotic drugs, such as clozapine and haloperidol, have been found to enhance latent inhibition (LI) in humans and rats. LI is a process of learning to ignore irrelevant stimuli that is disrupted in acute, positive-symptom schizophrenia, and can be modelled in animals. OBJECTIVES: The aim of this study was to determine the effects of two selective 5-HT(2A) receptor antagonists, SR 46,349B and ICI 169,369, on LI, as a test of their antipsychotic potential. METHODS: Doses of the 5-HT(2A) receptor antagonists that were sufficient for receptor blockade were determined in 5-HT behavioural syndrome tests. SR 46,349B and ICI 169,369 were then tested for enhancement of LI and reversal of amphetamine-induced attenuation of LI in a conditioned suppression paradigm. RESULTS: SR 46,349B (0.6-2.4 mg kg(-1) i.p.) and ICI 169,369 (10-40 mg kg(-1) i.p.) antagonised 5-hydroxytryptophan (5-HTP)-induced head twitches and wet dog shakes, which are mediated by 5-HT(2A) receptors, but had no effect on mCPP-induced hypolocomotion, which is mediated by 5-HT(2C) receptors. Neither SR 46,349B (1.2 mg kg(-1) i.p.) nor ICI 169,369 (40 mg kg(-1) i.p) affected 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT)-induced forepaw treading, suggesting that they were not in vivo 5-HT(1A) receptor antagonists. SR 46,349B (2.4 mg kg(-1) i.p.) and ICI 169,369 (40 mg kg(-1) i.p.) enhanced LI when given at both the pre-exposure and conditioning stages of the paradigm, but not when given at either pre-exposure or conditioning only. Both drugs also reversed the disruption of LI induced by D-amphetamine (1 mg kg(-1) i.p.). CONCLUSIONS: The profile of SR 46,349B and ICI 169,369 in LI differs from that of clozapine and haloperidol in LI, which both enhance LI when given only at the conditioning stage of the paradigm.