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  • 1
    Electronic Resource
    Electronic Resource
    Low doses of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH DPAT) increase ethanol intake (1994)
    Springer
    Psychopharmacology 115 (1994), S. 173-179 
    Details
    ISSN: 1432-2072
    Keywords: Limited access schedule ; Ethanol intake ; 8-OH DPAT ; Behaviour ; 5-HT ; Water deprivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous work has reported that the 5-hydroxytryptamine (5-HT)1A agonist, 8-hydroxy 2-(di-n-propylamino)tetralin (8-OH DPAT), reduces ethanol intake by rats. However, as 8-OH DPAT reduces 5-HT neurotransmission, these findings are inconsistent with the proposed inhibitory role of central 5-HT neurons on ethanol intake. We examined the effect of 8-OH DPAT on ethanol, water and food intake in rats maintained on a limited access schedule using a lower dose range (6–250 µg/kg) and by assessing concomitant changes in behaviour. Low doses of 8-OH DPAT enhanced ethanol intake even when food and water were offered as alternatives. Suppression in ethanol intake was observed at higher doses where elements of the 5-HT syndrome were apparent. Similar observations were made in both fluid and non-fluid deprived water drinking rats, suggesting the latter effect is non-selective. Therefore 8-OH DPAT may both increase or decrease ethanol consumption in the rat depending on the dose used.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244769
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  • 2
    Electronic Resource
    Electronic Resource
    Conditioned place preference induced by microinjection of 8-OH-DPAT into the dorsal or median raphe nucleus (1993)
    Springer
    Psychopharmacology 113 (1993), S. 31-36 
    Details
    ISSN: 1432-2072
    Keywords: Conditioned place preference ; 8-OH-DPAT ; Dorsal raphe ; Median raphe ; 5-Hydroxytryptamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Experiments were conducted to examine the ability of the selective 5-hydroxytryptamine (5-HT)1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) to induce a conditioned place preference following peripheral injection, and direct microinjection into the dorsal or median raphe nuclei. An unbiased place preference paradigm was used in which control animals showed no preference for either of two compartments differing in terms of colour (white versus black), floor texture (rough versus smooth) and olfactory cues (no odour versus acetic acid odour). Drug treatments were paired with access to either of the two compartments, and saline injections were paired with access to the other compartment. Rats experiencing a low dose of 8-OH-DPAT (125 µg/kg) with a specific compartment demonstrated a significant preference for that compartment over one paired with saline injections. The magnitude of this effect was similar to that observed in rats treated with 1.5 mg/kgd-amphetamine. A significant place preference was found in animals receiving injections of 8-OH-DPAT in the dorsal raphe at 0.1 µg but not 1 µg. Animals also displayed a preference for the compartment paired with 1 µg 8-OH-DPAT injected into the median raphe; lower doses were not effective. These results indicate that the mechanism by which 8-OH-DPAT induces a conditioned place preference involves activation of raphe somatodendritic 5-HT1A autoreceptors, leading to a reduction in 5-HT neurotransmission. This demonstration of the rewarding properties of 8-OH-DPAT, together with previous results showing increased feeding and sexual behaviour following 8-OH-DPAT treatment, strongly suggests an important role for brain 5-HT systems in reward and reinforcement processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244330
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  • 3
    Electronic Resource
    Electronic Resource
    Influence of 5-HT3 receptor antagonists and the indirect 5-HT agonist, dexfenfluramine, on heroin self-administration in rats (1994)
    Springer
    Psychopharmacology 114 (1994), S. 611-619 
    Details
    ISSN: 1432-2072
    Keywords: Heroin self-administration ; Rat ; 5-HT ; 2-HT3 receptor antagonists ; Ondansetron ; MDL72222 ; Indirect 5-HT agonist ; Dexfenfluramine ; Opioid reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the present study was to examine the effects of the 5-HT3 antagonists ondansetron and MDL72222, and the 5-HT releaser and reuptake inhibitor dexfenfluramine, on intravenous heroin self-administration by Wistar rats. Using separate squads of animals, two separate schedules of heroin reinforcement were used; a relatively low dose (0.03 mg/kg per infusion) made available under a FR5 schedule for 1 h each day, and a moderate heroin dose (0.1 mg/kg per infusion) available under a FR1 schedule for 2 h each day. Following the acquisition of stable levels of responding across days, both naloxone pretreatment (0.25 mg/kg SC) and halving the heroin infusion dose produced increases in operant responding for heroin at each concentration. Neither ondansetron (0.01–1 mg/kg SC) nor MDL72222 (0.1–3 mg/kg SC) pretreatment influenced heroin self-administration. Chronic treatment (5 day) of ondansetron (0.01–0.1 mg/kg) was similarly ineffective. However, dexfenfluramine (0.5–2.5 mg/kg IP) consistently reduced heroin self-administration at doses producing only modest decreases in food responding. These findings are in contrast to place conditioning studies, which show that 5-HT3 antagonists but not indirect 5-HT agonists block a morphine-induced place preference. Reasons for such discrepancies remain to be determined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244992
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of 5-HT3 receptor antagonists on the discriminative stimulus properties of morphine in rats (1993)
    Springer
    Psychopharmacology 112 (1993), S. 111-115 
    Details
    ISSN: 1432-2072
    Keywords: Morphine drug discrimination ; Rat ; 5-HT3 receptor antagonists ; Opioid ; Naloxone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 5-HT3 receptor antagonists, e.g. MDL72222, ondansetron and ICS205-930, have been previously reported to block a morphine (1.5 mg/kg)-induced conditioned place preference in rats. This finding suggests that these drugs may modify the morphine discriminative stimulus which underlies place conditioning. To study this further we have examined the effects of MDL72222, ondansetron and ICS205-930 against a morphine discriminative stimulus using a two-choice, food reinforced, operant paradigm. In an attempt to provide consistency with previous place conditioning studies, a morphine training dose of 1.5 mg/kg was used in addition to a higher 3 mg/kg dose which was studied in separate animals. Stimulus control of behaviour was attained at both morphine training doses, the characteristics of each being consistent with an effect at the mu opioid receptor. Ondansetron (0.001–1 mg/kg), MDL72222 (0.1–3 mg/kg), and ICS205-930 (0.001–1 mg/kg) all failed to consistently antagonise the morphine cue at both training doses, although a mild attenuation was seen in the 1.5 mg/kg group following pretreatment with an intermediate dose of ondansetron and ICS205-930 (both 0.01 mg/kg). The present results therefore suggest hat 5-HT3 antagonists do not block a morphine discriminative state, at least in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02247370
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  • 5
    Electronic Resource
    Electronic Resource
    Differential effects of ondansetron and α-flupenthixol on responding for conditioned reward (1997)
    Springer
    Psychopharmacology 134 (1997), S. 64-72 
    Details
    ISSN: 1432-2072
    Keywords: Key words Ondansetron ; d-Amphetamine ; α-Flupenthixol ; Nucleus accumbens ; Conditioned reward
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous experiments have suggested that 5-HT3 antagonists such as ondansetron may alter reward-related behaviour that is dependent in part upon raised mesolimbic dopamine activity. However, the evidence for this is far from conclusive. One major behavioural role of dopamine is in the control of behaviour elicited by conditioned rewarding stimuli. To date, the effects of 5-HT3 antagonists on this function of mesolimbic dopamine have not been examined. Two experimental procedures were employed to examine the effects of ondansetron (10 and 100 μg/kg) on the acquisition of responding for conditioned reward, and on the response potentiating effect of intra-accumbens d-amphetamine (10 μg). These effects were compared to those elicited by the dopamine antagonist α-flupenthixol (0.1 mg/kg). In the first procedure, rats were trained to associate food pellet delivery with a conditioned stimulus (CS). Rats subsequently allowed to respond on a lever delivering this CS, and on an inactive lever, showed a greater preference for the lever delivering the CS, indicating that this CS functioned as a conditioned reward (CR). Ondansetron administered during the conditioning phase did not alter subsequent responding for the CR, but α-flupenthixol induced a small but significant reduction in responding on the CR lever. These results suggest that blockade of dopamine receptors, but not 5-HT3 receptors interfere with the learning of stimulus reward relationships. In the second procedure, d-amphetamine injected into the nucleus accumbens markedly potentiated responding for CR. Ondansetron at 10 μg/kg induced a small attenuation of this effect, without altering responding in its own right. However, at a higher dose (100 μg/kg) ondansetron plus amphetamine treatment significantly enhanced responding on the inactive lever. At both doses, the net effect of ondansetron was to produce a subtle impairment in the allocation of responses such that the differential responding on the CR versus NCR lever was diminished. In contrast to these effects α-flupenthixol significantly attenuated d-amphetamine’s selective enhancement of responding for conditioned reward, as well as impairing the ability of the conditioned reward to elicit and maintain behaviour. These results confirm the role of dopamine in responding for conditioned reward, and suggest a possible modulators role for 5-HT3 receptors in this process. However, the effects of ondansetron on the acquisition of, and responding for, conditioned reward are clearly different from those induced by blockade of dopamine receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050426
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  • 6
    Electronic Resource
    Electronic Resource
    Effects of 5-HT3 receptor antagonists on behavioural measures of naloxone-precipitated opioid withdrawal (1991)
    Springer
    Psychopharmacology 105 (1991), S. 322-328 
    Details
    ISSN: 1432-2072
    Keywords: Opioid withdrawal ; 5-HT3 receptor ; Ondansetron ; MDL 72222 ; Rat ; Place aversion ; Withdrawal syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of the selective 5-HT3 receptor antagonists, ondansetron and MDL 72222, against various behaviours elicited by naloxone-precipitated morphine withdrawal were examined. Rats made dependent upon morphine by the subcutaneous implantation of a 75 mg pellet, when challenged with naloxone (0.5 mg/kg SC), 3 or 4 days later exhibited a wide range of behaviours including wet dog shakes, paw shakes, salivation and a marked weight loss. Pre-treatment with ondansetron (0.01–1 mg/kg SC) or MDL 72222 (1–3 mg/kg SC) failed to affect the incidence of these responses except weight loss, which was attenuated by both treatments. At doses similar to and below those required to elicit the withdrawal syndrome, naloxone produced a single-trial place aversion in morphine dependent rats. The place aversion produced by naloxone (0.05 mg/kg SC) was antagonized by pre-treatment of ondansetron (0.1–1 mg/kg SC) and MDL 72222 (1 mg/kg SC) prior to conditioning. Chlordiazepoxide (10 mg/kg IP) but not gepirone (3–10 mg/kg SC) was similarly effective. It is concluded that 5-HT3 antagonists may attenuate some but not all behavioural signs associated with morphine withdrawal. Reasons for this apparent selectivity are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244425
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  • 7
    Electronic Resource
    Electronic Resource
    Effect of the 5-HT3 receptor antagonists, MDL72222 and ondansetron on morphine place conditioning (1992)
    Springer
    Psychopharmacology 106 (1992), S. 315-320 
    Details
    ISSN: 1432-2072
    Keywords: Morphine ; 5-HT3 receptor ; Ondansetron ; MDL72222 ; Rat ; Place conditioning ; Reward
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the present study was to reassess the original findings of Carboni et al. (1988) who suggested that 5-HT3 receptor antagonists may block morphine-induced place conditioning in rats. These workers used a biased protocol with treatments allocated to compartments based on initial preference. In the present study we have adopted an unbiased approach with treatments randomly assigned to conditioning compartment in a counter-balanced fashion. Thus treatments were equally paired between distinct environmental cues. Using this protocol, morphine produced a dose-related place preference (0.3–3 mg/kg SC). Thirty-minute pretreatment with the selective 5-HT3 antagonists, MDL72222 (1 mg/kg SC) and ondansetron (0.01 mg/kg SC) before morphine (1.5 mg/kg SC), significantly antagonized the place conditioning to this treatment. However, with higher doses of ondansetron (0.1–1 mg/kg SC), the antagonism of morphine-induced place preference became variable and dependent on the conditioning compartment. This was probably a reflection of the fact that ondansetron when administered alone also appeared to produce an environmentally dependent place conditioning at these doses. Therefore it is concluded that at certain doses, 5-HT3 receptor antagonists may antagonize morphine place conditioning in a manner consistent with a blockade of the appetitive effects of this drug. However, at higher doses, at least with ondansetron, this antagonism became non-specific and dependent on the training environment. It is suggested that other animal models of opioid reinforcement (e.g., self-administration) are now needed to validate the hypothesis that 5-HT3 receptor antagonists may modify opioid reward.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245411
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  • 8
    Electronic Resource
    Electronic Resource
    Evidence that the amygdala is involved in the disinhibitory effects of 5-HT3 receptor antagonists (1991)
    Springer
    Psychopharmacology 104 (1991), S. 545-551 
    Details
    ISSN: 1432-2072
    Keywords: 5-HT3 receptors ; Amygdala ; Dorsal raphe nucleus ; Ondansetron ; Granisetron ; Social interaction ; Water-lick conflict test ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of various 5-HT3 receptor antagonists were examined in the social interaction (SI) test following discrete microinjection into either the dorsal raphe nucleus (DRN) or amygdala of the rat. Following DRN injection, ondansetron, ICS205-930, and MDL72222 (5–500 ng) all failed to modify SI under high light/unfamiliar (HLU) test conditions relative to vehicle pretreated controls. The 5-HT3 receptor agonist, 2-Me 5-HT (100–2500 ng), was similarly ineffective under both HLU and low light/familiar (LLF) conditions, although 5-HT (20–100 ng) increased SI under the HLU paradigm. After amygdaloid injection, ondansetron (10–100 ng), granisetron (1–10 ng), ICS205-930 (10–100 ng), GR 65630 (1–10 ng), and MDL72222 (100–1000 ng) all significantly increased SI under the HLU but not LLF condition. Furthermore, a detailed behavioural analysis revealed that the behaviours underlying this increase were similar to those seen in vehicle pretreated animals tested in the LLF compared to HLU condition. The benzodiazepine, flurazepam (200 ng), increased both SI (HLU condition) and punished responding in a modified water-lick conflict model, after amygdaloid injection. Both ondansetron (10–1000 ng) and ICS205-930 (1–100 ng) were ineffective in the conflict test. Finally, 2-Me 5-HT and 5-HT (100–10 000 ng) reduced SI under the LLF test condition with no concomitant change in locomotor activity. It is concluded that the amygdala, but not the DRN, may represent an important neuroanatomical locus for the disinhibitory, perhaps anxiolytic, properties of 5-HT3 receptor antagonists.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245664
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