Biomedical subjects

A J Greenshaw

Publications and source records attributed to A J Greenshaw.

At least 19 recordsLinked to original sources

PubMed2006

Aversive stimulus properties of the 5-HT2C receptor agonist WAY 161503 in rats.

Serotonin2C (5-HT2C) receptors may influence motivation and reward through effects on the mesocorticolimbic dopamine (DA) system. Previous work from this laboratory indicated that 5-HT2C receptor stimulation does not induce place conditioning when animals are tested in a drug-free state, but does result in decreased locomotor activity and increased frequency thresholds for electrical self-stimulation of the ventral tegmental area (VTA). The present study was conducted to determine whether the 5-HT2C receptor agonist WAY 161503 may induce place conditioning in a state-dependent manner and also whether this compound will induce gustatory avoidance conditioning in the conditioned taste aversion (CTA) paradigm. The effects of the 5-HT2C receptor agonist WAY 161503 in the place conditioning and CTA (two-bottle choice test) paradigms were assessed in male Sprague-Dawley rats. Administration of WAY 161503 (3.0 mg/kg) induced a state-dependent conditioned place aversion and a CTA to saccharin. The differential state dependency of 5-HT2C receptor agonists' effects in place conditioning (state dependent) and CTA (non-state dependent) is consistent with the activation of different brain systems in these two paradigms. The state-dependent effects in place conditioning underscore the need to include controls for state dependency in studies of 5-HT receptor related compounds.

Amphetamine↗

PubMed2005

Facilitation of brain stimulation reward by MK-801 (dizocilpine) may be independent of D2-like dopamine receptor stimulation in rats.

RATIONALE: Dopamine (DA) and glutamate (Glu) interactions in the mesocorticolimbic pathway may regulate motivation and reward and contribute to schizophrenia and drug abuse. We have recently demonstrated synergistic effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor blockade and D(2/3) DA receptor stimulation in brain stimulation reward (BSR). OBJECTIVES: This study was conducted to explore interactions between DA and Glu systems in BSR using the NMDA receptor antagonist MK-801 and the DA receptor agonists 7-OH-DPAT and apomorphine. METHODS: Systemic effects of these compounds were measured in male Sprague-Dawley rats using rate-frequency threshold analysis of ventral tegmental area (VTA) BSR (n=27). Effects of bilateral applications of MK-801 and 7-OH-DPAT into the nucleus accumbens (NAS) shell subregion were also investigated (n=10). RESULTS: MK-801 (0.03 or 0.13 mg kg(-1) i.p. or 0.66 mug intra-NAS) reduced reward thresholds while 7-OH-DPAT (0.03 mg kg(-1) s.c. or 5.0 microg intra-NAS) or apomorphine (0.05 mg kg(-1), s.c.) increased this measure. MK-801 combined with apomorphine or with 7-OH-DPAT, systemically or in the NAS shell, induced additive effects. CONCLUSIONS: Lack of interaction between DA agonists and MK-801 in this study contrasts with our previous work showing synergistic reward-decreased effects of AMPA/kainate receptor blockade and D(2/3) DA receptor stimulation in the NAS shell, and indicates possible independence of DA and N-methyl-D-aspartate (NMDA) receptor effects in VTA electrical self-stimulation.

Animals↗

PubMed2004

Differential effects of intra-midbrain raphe and systemic 8-OH-DPAT on VTA self-stimulation thresholds in rats.

RATIONALE: Intra-median raphe nucleus (MRN) administration of the 5-HT(1A) receptor agonist 8-OH-DPAT decreases lateral hypothalamic self-stimulation thresholds and is reported to have biphasic effects following systemic administration. These experiments attempted to extend the previous findings to mesolimbic pathway self-stimulation at ventral tegmental area (VTA) electrodes. OBJECTIVES: This study was conducted to provide comparative data for systemic and intra-dorsal raphe nucleus (DRN) and intra-MRN effects of 8-OH-DPAT on VTA self-stimulation. METHODS: Male Sprague-Dawley rats with VTA electrodes were trained to respond for electrical stimulation. Systemic and intra-midbrain raphe 8-OH-DPAT effects on rate-frequency thresholds were measured. Systemic administration of WAY 100635 was used to confirm 5-HT(1A) receptor mediation of 8-OH-DPAT effects. RESULTS: 8-OH-DPAT (0.003-0.3 mg kg(-1) SC) increased rate-frequency thresholds and decreased maximal response rates. WAY 100635 alone (0.0125-0.1 mg kg(-1) SC) did not alter these measures. Intra-DRN and intra-MRN 8-OH-DPAT (5.0 microg) decreased rate-frequency thresholds without altering maximal response rates. Intra-DRN 8-OH-DPAT (0.1-5.0 microg) induced a slight decrease and intra-MRN 8-OH-DPAT a slight increase in locomotor activity. WAY 100635 (0.1 mg kg(-1)) blocked effects of 8-OH-DPAT on VTA self-stimulation. CONCLUSION: These results confirm threshold-decreasing effects of intra-MRN 8-OH-DPAT and extend this to the DRN and to VTA thresholds. Monophasic dose dependent increases in VTA thresholds following systemic 8-OH-DPAT are not equivalent to reports for hypothalamic self-stimulation. Differences between studies may be attributable to stimulation site and/or differences in threshold measurement procedures. Effects of WAY 100635 in this study indicate 5-HT(1A) receptor mediation of these 8-OH-DPAT effects.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2002

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.

Amphetamine↗

PubMed2001

Common effects of chronically administered antipanic drugs on brainstem GABA(A) receptor subunit gene expression.

Panic disorder is an anxiety disorder that can be treated by long-term administration of tricyclic antidepressants such as imipramine, monoamine oxidase inhibitors such as phenelzine, or the selective serotonin reuptake inhibitor (SSRI) antidepressants. Clinical data also indicate that some benzodiazepines, such as alprazolam, are effective antipanic agents, and that their therapeutic onset is faster than that of antidepressants. Benzodiazepines are well known for their action at GABA(A) receptors, and preclinical data indicate that imipramine and phenelzine also interfere with the GABAergic system. In addition some clinical data lend support to decreased benzodiazepine-sensitive receptor function in panic disorder patients. Using imipramine, phenelzine and alprazolam, we investigated, in rats, the possibility that the therapeutic efficacy of antipanic agents stems from the remodeling of GABAergic transmission in the pons-medulla region. Of the 12 GABA(A) receptor subunit (alpha 1--6, beta 1--3, gamma 1--3) steady-state mRNA levels investigated, we observed an increase in the levels of the alpha 3-, beta 1- and gamma 2-subunit transcripts with all three antipanic agents tested. The effects of imipramine and phenelzine on these subunits occurred after 21 days of treatment, while alprazolam effects were observed after 3 days of administration. Histochemical data suggest that the alpha 3 beta 1 gamma 2 subunits comprise a receptor subtype in the pons-medulla region. Therefore, we conclude that these molecular events parallel the therapeutic profile of the drugs examined. We further propose that these events may correspond to a remodeling of the GABA(A) receptor population, and may be useful markers for investigation of the antipanic properties of drugs.

Alprazolam↗

PubMed2000

Effects of AMPA/kainate receptor blockade on responses to dopamine receptor agonists in the core and shell of the rat nucleus accumbens.

The present experiments were conducted to investigate effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazoleprionic acid (AMPA)/kainate receptor blockade (CNQX, NBQX) on locomotor responses to D2/3 (7-OH-DPAT) and D1 [(+)-SKF 38393] dopamine receptor agonists in the nucleus accumbens (NAS) core and shell. CNQX (0.25-0.5 microgram) microinjected into the NAS core or shell did not affect baseline locomotor activity. 7-OH-DPAT (2.5-5 micrograms) decreased locomotor activity. Co-administration of CNQX (0.5 microgram) increased the effects of 7-OH-DPAT (5 micrograms) in the NAS core and shell. A similar increase was observed with NBQX (0.5 microgram) in the NAS shell. (+)-SKF 38393 (5 micrograms) into the NAS core and shell increased locomotor activity after 30 min; this effect was not altered by CNQX (0.5 microgram). As the D2/3 dopamine agonist (-)-quinpirole (2 micrograms) increased effects of (+)-SKF 38393 (5 micrograms) in NAS shell but not core, lack of site-selective effects of (+)-SKF-38393 and of 7-OH-DPAT within NAS is not attributable to drug diffusion. The previous observation that glutamate effects on locomotor activity depend on the relative involvement of D1 or D2/3 dopamine receptors in the NAS was based on the dopamine-depletion model. The present results demonstrate differential interactions of AMPA receptor blockade with dopamine agonists in "dopamine-intact" animals.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2000

Comparison of neurochemical effects of the monoamine oxidase inhibitors phenelzine, moclobemide and brofaromine in the rat after short- and long-term administration.

BACKGROUND: Chronic administration of several irreversible monoamine oxidase (MAO) inhibitors induces a down-regulation of tryptamine and 5-hydroxytryptamine(2) receptors in rat brain, but there is a paucity of information available on the effects of reversible MAO-A inhibitors on these receptors. METHODS: Acute and chronic experiments were conducted in rats and the effects of the irreversible monoamine oxidase inhibitor, phenelzine and the reversible MAO type-A inhibitors, moclobemide and brofaromine, on tryptamine and 5-hydroxytryptamine(2) receptors were analysed using radioligand binding techniques. In addition, activities of MAO-A and -B were determined radiochemically and brain and/or urine levels of tryptamine, 5-hydroxytryptamine, 3-methoxy-4-hydroxyphenylglycol (MHPG), beta-phenylethylamine, brofaromine and moclobemide were determined by chromatographic procedures. RESULTS: After 30 days of administration, moclobemide and brofaromine selectively inhibited brain MAO-A activity and phenelzine inhibited MAO-A and -B to equal extents. All three drugs caused a significant down-regulation of tryptamine receptors, whereas only phenelzine significantly down-regulated 5-hydroxytryptamine(2) receptors. In a comparison of phenelzine and brofaromine, both caused marked elevations of urinary tryptamine and decreases of urinary MHPG levels, while only phenelzine increased beta-phenylethylamine levels. After 14 days of administration, phenelzine, but not moclobemide or brofaromine, significantly increased levels of tryptamine in brain; all three drugs significantly increased 5-HT levels. LIMITATIONS: 24-h urine samples were not collected for moclobemide-treated animals and brain levels of tryptamine were not measured after 30-day administration. CONCLUSIONS: These studies revealed marked neurochemical differences among phenelzine, moclobemide and brofaromine which could contribute to their actions in the clinical setting.

Animals↗

PubMed2000

Subchronic fluoxetine treatment induces a transient potentiation of amphetamine-induced hyperlocomotion: possible pharmacokinetic interaction.

The results of the present study show that 5 days of systemic treatment with fluoxetine (5 mg/kg) resulted in an augmented locomotor response to amphetamine (0.5 mg/kg). This augmented response to amphetamine was observed 24 and 48 h, but not 5 days, after the cessation of fluoxetine treatment. Subchronic fluoxetine treatment also produced an increase in the brain concentration of amphetamine when rats were challenged with amphetamine 48 h, but not 5 days, after the cessation of fluoxetine treatment. Thus, the effect of subchronic fluoxetine in augmenting amphetamine-induced hyperactivity was consistent with the effect of subchronic fluoxetine in augmenting the amphetamine concentration in the brain. This pattern of results indicates that subchronic fluoxetine potentiates the response to amphetamine within a limited time-window, and that this potentiating effect is likely to be due to the reduced metabolism of amphetamine via the inhibition of cytochrome P450 by fluoxetine and/or its metabolite norfluoxetine.

Amphetamine↗

PubMed2000

Neurochemical and metabolic aspects of antidepressants: an overview.

Antidepressants, in addition to being effective therapeutic agents for depression, have also proved to be multifaceted drugs useful for treating a number of other psychiatric and neurologic disorders. Despite the widespread use of these drugs, much remains to be understood about their mechanisms of action and other important aspects, such as their metabolism and potential interactions with other drugs. This article reviews research conducted in the authors' laboratories on various aspects of antidepressants, including trace amines and antidepressants, gamma-aminobutyric acid and antidepressants, drug metabolism, development and application of rapid, sensitive assay procedures for antidepressants and their metabolites; and drug development based on analogues of the antidepressants phenelzine and tranylcypromine. The significance of this work to future drug development is also discussed.

Animals↗

PubMed1999

Acute fluoxetine treatment potentiates amphetamine hyperactivity and amphetamine-induced nucleus accumbens dopamine release: possible pharmacokinetic interaction.

Amphetamine stimulates locomotor activity, in large part by activating central dopaminergic systems. Serotonin shares on overlapping distribution with dopamine and has been shown to modulate dopaminergic function and dopamine-mediated behaviors. The present study examined whether increasing serotonergic function, via the selective serotonin reuptake inhibitor fluoxetine, would alter the stimulatory effects of amphetamine on locomotor activity and dopamine overflow in the nucleus accumbens. In addition, the present study determined whether fluoxetine treatment would alter the metabolism of amphetamine. Results show that 5.0 mg/kg fluoxetine potentiated the locomotor activity induced by amphetamine (0.5-1.0 mg/ kg), and enhanced the increased dopamine overflow in the nucleus accumbens induced by amphetamine. Fluoxetine treatment also resulted in a higher concentration of amphetamine in the CNS. Together, these findings indicate that acute fluoxetine treatment potentiates the locomotor stimulating and dopamine activating effects of amphetamine. Further, the results indicate that fluoxetine potentiates the effects of amphetamine by decreasing the metabolism of amphetamine, probably through inhibition of cytochrome P450 isozymes.

Adrenergic Uptake Inhibitors↗

PubMed1999

The potentiating effect of sertraline and fluoxetine on amphetamine-induced locomotor activity is not mediated by serotonin.

Sertraline dose-dependently increased the locomotor stimulating effect of amphetamine. At the highest dose, 20 mg/kg sertraline had a biphasic effect on amphetamine-induced hyperactivity, producing an initial reduction in amphetamine-induced hyperactivity that was later followed by an augmentation of amphetamine-induced hyperactivity in the last hour of the 3-h test. Sertraline, at doses of 5 and 10 mg/kg, produced an augmentation of amphetamine-induced hyperactivity over the last 2 h of the 3-h test session. Further, there was an increase in the concentration of amphetamine in the brain in rats pretreated with 5 mg/kg sertraline. Both sertraline (5 mg/kg) and fluoxetine (5 mg/kg) produced an augmentation of amphetamine-induced hyperactivity that was unaltered by a serotonergic lesion of the median and dorsal raphe nuclei that resulted in a greater than 90% depletion of serotonin in hippocampus, striatum, and nucleus accumbens. Further, both sertraline and fluoxetine inhibited spontaneous locomotor activity and this effect was also unaltered by the depletion of serotonin. Thus, serotonergic neurotransmission is not essential for the effects of sertraline and fluoxetine on spontaneous and amphetamine-induced locomotion. It is probable that sertraline and fluoxetine augment the locomotor stimulatory effect of amphetamine by decreasing the metabolism of amphetamine, perhaps via actions on cytochrome P450 isozymes.

Amphetamine↗

PubMed1999

American ginseng extract reduces scopolamine-induced amnesia in a spatial learning task.

OBJECTIVE: To determine if HT-1001, an extract of American ginseng, affects scopolamine-induced memory and performance deficits in a spatial learning task, alters brain concentrations of aminergic neurotransmitters, and alters choline uptake in synaptosome preparations. DESIGN: Animal study. ANIMALS: 48 Sprague Dawley rats. INTERVENTIONS: Long-term oral administration of a test material or control solution. Intraperitoneal administration of scopolamine (2 mg/kg) 30 minutes before testing. OUTCOME MEASURES: Performance on Morris water maze task, choline uptake, aminergic neurotransmitter analysis, in vitro monoamine oxidase analysis (of compounds). RESULTS: HT-1001 protected against scopolamine-induced amnesia and increased choline uptake in synaptosomal preparations. HT-1001 did not alter brain concentrations of norepinephrine, dopamine, 5-HT (serotonin), 3,4-dihydroxyphenylacetic acid or 5-hydroxyindoleactic acid. HT-1001 had a very weak ability to inhibit monoamine oxidase activity in vitro. CONCLUSIONS: HT-1001 demonstrates a capacity to protect against scopolamine-induced memory deficits.

Animals↗

PubMed1997

A simple technique for determining stereotaxic coordinates for brain implantation of probes at rotated angles in one or two planes.

A simple method for deriving stereotaxic coordinates for angular approaches to brain target sites is described. This method requires the use of a stereotaxic instrument with two micromanipulators and is based on the relative measurement of stereotaxic zero and the target site. This is achieved using a conventional (perpendicular) angle of approach with a probe held in one micromanipulator to visually guide the placement of the angled micromanipulator which holds a second probe. The technique may be used to derive angular approach coordinates for any angle in the coronal and/or sagittal planes. Once the coordinates are derived, they may be used with a single micromanipulator, as in the case of conventional placements. The derivation of the angular approach coordinates involves simple subtraction; no trigonometrical calculations are used. This method is simple and efficient.

Animals↗

PubMed1997

Nicotine-induced decreases in VTA electrical self-stimulation thresholds: blockade by haloperidol and mecamylamine but not scopolamine or ondansetron.

The effects of repeated daily injections of (-)-nicotine (+) hydrogen tartrate (mg kg-1 s.c.) on electrical self-stimulation of the ventral tegmental area were investigated. Nicotine reduced the frequency required to maintain half-maximal response rates with animals responding in rate-frequency threshold tests. Under these conditions, nicotine induced an increase in the total number of self-stimulation responses per session, but had no statistically significant effects on the maximal response rate. These effects of nicotine were observed by the second day of administration of this drug. Acute injections of the D2-like dopamine receptor antagonist haloperidol (0.03 mg kg-1 s.c.) and of the nicotinic acetylcholine receptor antagonist mecamylamine (1 mg kg-1 s.c.) attenuated the effects of nicotine, indicating that the observed effects involve stimulation of D2-like dopamine receptors as a result of nicotinic receptor activation. The muscarinic acetylcholine receptor antagonist scopolamine (3 mg kg-1 s.c.) and the serotonin 5-HT3 receptor antagonist ondansetron (0.01 and 0.1 mg kg-1 s.c.) did not alter the effects of nicotine. The results of this study indicate that repeated daily administration of (-)-nicotine increases the rewarding effects of electrical self-stimulation of the ventral tegmental area. These data are consistent with the proposal that repeated daily injections of nicotine positively effect a mesolimbic dopaminergic substrate of reward.

Animals↗

PubMed1997

The non-antiemetic uses of serotonin 5-HT3 receptor antagonists. Clinical pharmacology and therapeutic applications.

The discovery of multiple subtypes of the serotonin 5-HT receptor has generated enormous interest over the past few years. Possibly the most exciting, in terms of psychiatric clinical practice, appeared to be the 5-HT3 receptor. Early animal studies suggested that the 5-HT3 receptor antagonists, in addition to their well recognised antiemetic use, might be clinically useful in a number of areas. These included anxiety disorders, psychotic disorders, drug and alcohol abuse disorders, depressive disorders, cognitive disorders, the treatment of pain and the treatment of irritable bowel syndrome. With the exception of antiemetic actions, this review examines these potential therapeutic areas carefully, paying particular attention not only to the animal literature, but to the clinical studies which have resulted from these initial findings. Unfortunately, studies in many of these therapeutic areas have not lived up to their initial promise. Indeed, no clinical studies have yet clearly demonstrated the usefulness of 5-HT3 receptor antagonists in the treatment of CNS disorders. Nonetheless, in view of the absence of published results from double-blind, placebo-controlled studies in many of these therapeutic areas, further research would be useful in confirming the effectiveness, or otherwise, of this group of compounds.

Analgesics↗

PubMed1996

Chronic administration of antipanic drugs alters rat brainstem GABAA receptor subunit mRNA levels.

Mental illness, such as panic disorder and depression, display comorbidity as well as common therapeutic treatments. These features point toward a common etiology and/or therapeutic pathway. There is evidence to suggest that some antipanic agents may mediate their effects by altering gamma-aminobutyric acid (GABA) levels or by modulating the activity of the GABAA receptor. Chronic stimulation of GABAA receptors by agonists or modulators results in changes in the pharmacological properties of the receptor concomitant with alterations in the expression of specific GABAA receptor subunits. Therefore, we investigated the hypothesis that long-term exposure to three antidepressant/antipanic drugs (imipramine, phenelzine and alprazolam) would produce changes in the steady-state levels of those subunit mRNAs that are believed to encode the major GABAA receptor subtype. Further, these changes in gene expression would be different to those produced by the non-antipanic anxiolytic (buspirone). We report here that, following a 21 day treatment, imipramine, phenelzine, alprazolam and buspirone differentially altered rat brainstem levels of GABAA receptor alpha 1-, beta 2- and gamma 2-subunit RNAs. These results demonstrate novel actions of antidepressant/antipanic drugs on GABAergic neurotransmission.

Animals↗

PubMed1995

Behavioural response to SKF 38393 and quinpirole following chronic antidepressant treatment.

The effects of chronic administration of antidepressant drugs (21-22 days s.c. via osmotic mini-pumps) on the behavioural responses of male Sprague-Dawley rats to (-)-quinpirole hydrochloride (0.05 mg kg-1 s.c., 5 min) and (+/-)-SKF 38393 hydrochloride (10 mg kg-1 s.c., 5 min) were investigated. Desipramine hydrochloride (10 mg kg-1 per day), phenelzine sulphate (10 mg kg-1 per day) and clorgyline hydrochloride (1 mg kg-1 per day) attenuated the suppression of locomotor activity induced by quinpirole, a dopamine D2-like receptor agonist, while clomipramine hydrochloride (10 mg kg-1 per day) was without effect. Yawning elicited by quinpirole was absent in phenelzine- and clorgyline-treated rats, but unaffected in rats treated chronically with desipramine and clomipramine. SKF 38393, a dopamine D1-like receptor agonist, significantly increased locomotor activity and time spent grooming in control animals. There were no significant effects of antidepressants on the behavioural responses to SKF 38393.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1995

5HT3 receptor antagonists do not block nicotine induced hyperactivity in rats.

The effects of 5-HT3 receptor antagonists (ondansetron 0.1 mg kg-1 SC 30 min; bemesetron 0.03 mg kg-1 SC 45 min) on nicotine-induced increases in locomotor activity were measured in male Sprague-Dawley rats. Intermittent daily injections of nicotine (0.3-1.2 mg kg-1 SC 30 min) resulted in increased locomotor activity as measured by photocell counts. The effect of nicotine was not affected by administration of the 5-HT3 receptor antagonists at doses that are reported to block nicotine- and morphine-induced place-preference conditioning. Neither of the 5-HT3 receptor antagonists tested affected activity counts in vehicle treated animals. Nicotine-induced hyperactivity was blocked by the dopamine antagonist haloperidol (0.03 mg kg-1 SC 2 h) and by the nicotinic antagonist mecamylamine (1 mg kg-1 SC 1 min). The effects of a range of doses (0-1 mg kg-1) of the 5-HT3 receptor antagonists ondansetron, bemesetron, granisetron and tropisetron on hyperactivity induced by 0.6 mg kg-1 nicotine were then assessed. Only tropisetron at 1 mg kg-1 attenuated nicotine-induced hyperactivity. To demonstrate the efficacy of the present range of doses of the 5-HT3 receptor antagonists in this study, conditioned taste aversion experiments were conducted. Ondansetron (0.1 mg kg-1) failed to attenuate a conditioned taste aversion to saccharin induced by nicotine (0.6 mg kg-1), but did induce a reduction in saccharin preference in choice tests following three saccharin-ondansetron pairings.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗