A 5-HT2C receptor antagonist potentiates a low dose amphetamine-induced conditioned place preference (original) (raw)
Related papers
Amphetamine-Induced Place Preference in Humans
Biological Psychiatry, 2009
Background-The conditioned place preference procedure is a widely used animal model of rewarding drug effects that, to date, has not been tested in humans. In this study, we sought to demonstrate that humans, like non-humans, would exhibit a preference for a place previously associated with amphetamine. Further, we investigated the relationship between conditioned place preference and the mood-altering effects of the drug. Methods-Thirty-one healthy individuals participated in a five-session procedure during which they experienced the effects of d-amphetamine (20mg) or placebo on two occasions in two distinctive environments (sessions 1 to 4). One group of subjects (paired group, N=19) received amphetamine consistently in one room and placebo in another room, while a second group (unpaired group, N=12) received amphetamine and placebo without regard to the rooms. During the sessions, participants completed questionnaires to rate their mood. On the fifth session, they rated their preference for the two rooms. Results-Individuals in the paired group rated their liking of the amphetamine-paired room significantly higher than the placebo-associated room, while there was no difference between ratings of the two rooms for individuals in the unpaired group. In the paired group, drug liking ratings during the conditioning sessions positively predicted preference for the drug-associated room, whereas reports of amphetamine-induced anxiety and dysphoria negatively predicted room liking scores. Conclusions-This study demonstrates that humans, like non-humans, prefer a place associated with amphetamine administration. These findings support the idea that subjective responses to a drug contribute to its ability to establish place conditioning.
Psychopharmacology, 1996
Amphetamine-induced place conditioning was evaluated in mice using a newly designed apparatus. It was demonstrated that this apparatus provides a neutral set of cues devoid of rewarding or aversive properties and can reveal place preference or aversion after pairings with drugs (amphetamine and morphine for preference and naloxone for aversion) known to produce such effects. Moreover, repeated pairings of environmental cues with either 2 or 3 mg/kg d-amphetamine resulted in significant conditioned place preference on a drug free test, whilst repeated pairings with a lower dose of the drug (1 mg/kg) resulted in significant conditioned place aversion. Finally, a small number of mice showed opposite responses in comparison with group means at low as well as at high doses of amphetamine. These results suggest that amphetamine may promote conditioned place preference or avoidance depending on dosage and individual susceptibility.
Psychopharmacology, 2002
Rationale: Changes in serotonin 1B (5-HT 1B ) receptor function appear to modify the reinforcing properties of cocaine, but the direction of this effect is not completely clear. Pharmacological stimulation of 5-HT 1B enhanced the rewarding properties of self-administered cocaine while attenuating the threshold-reducing effect of cocaine in the intracerebral brain stimulation procedure. Objective: The present study investigates how pharmacological modification of 5-HT 1B receptor-mediated neurotransmission influence cocaine motivational properties in the conditioned place preference paradigm in rats. Methods: In separate groups of rats the motivational properties of CP 94,253, a selective 5-HT 1B agonist, or GR 127935, a 5-HT 1B/D receptor partial agonist, given alone or in combination, were determined. To evaluate their influence on cocaine-induced place conditioning, CP 94,253, that was found to be aversive, was given every day before each conditioning session, while GR 127935, which given alone had no effect, was administered only before cocaine conditioning sessions. Results: CP 94,253, injected IP at 2.5 and 10 (but not 0.5) mg/kg produced place aversion in the place conditioning paradigm. The aversive effect of 2.5 mg/kg CP 94,253 was completely reversed by 10 mg/kg SC GR 127935. Given before every conditioning session, CP 94,253 did not modify place conditioning by four injections of 10 mg/kg cocaine but at 2.5 mg/kg it potentiated a sub-threshold dose of cocaine. The place preference caused by these two drugs was completely reversed by 10 mg/kg GR 127935. The antagonism by GR 127935 of CP 94,253's effects was shown not to be due to the induction of state-dependent effects. Conclusion: The results suggest that stimulation of 5-HT 1B receptors causes place aversion, and enhances the effect of low doses of cocaine in the conditioned place preference paradigm.
Differential effects of 5-HT2C receptor ligands on place conditioning and locomotor activity in rats
Effects of the 5-hydroxytryptamine (5-HT)(1A/1B/2C) receptor agonist N-[3-(trifluoromethyl)phenyl] piperazine (TFMPP, 0-3.0 mg/kg s.c.) and the 5-HT2C receptor agonist 8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]quinoxalin-5(6H)-one (WAY 161503, 0-3.0 mg/kg s.c.) in place conditioning were measured in male Sprague-Dawley rats. Effects of TFMPP, alone and with the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-2-pyridinyl-cyclohexanecarboxamine (WAY 100635), the 5-HT(1B) receptor antagonist N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-1,1'-biphenyl-4-carboxamide (GR 127935) or the 5-HT2C receptor antagonist 6-chloro-5-methyl-1-[[2-(2-methylpyrid-3-yloxy)pyrid-5-yl]carbamoyl]indoline (SB 242084) and of WAY 161503 alone and with SB 242084 on locomotor activity were also assessed. Neither TFMPP nor WAY 161503 induced place conditioning. WAY 161503 (1.0 and 3.0 mg/kg s.c.) decreased locomotor activity; SB 242084 (1.0 mg/kg i.p.) blocked this effect. Reduced locomotor activity following TFMPP was blocked by SB 242084 but not WAY 100635 (0.1 mg/kg s.c.) or GR 127935 (3.0 mg/kg s.c.). Behaviourally relevant levels of 5-HT2C receptor stimulation may not exert reinforcing effects, although other studies indicate that such manipulations alter reinforcing effects of drugs of abuse.
• The 5-HT 1D receptor agonist, PNU142633, attenuates METH-seeking behavior. • Preference for the METH-associated environment decreased in PNU + METH-primed rats. • PNU decreased LTP components in METH-primed rats. • PNU may decrease synaptic transmission and prevent METH reinstatement. A B S T R A C T Methamphetamine (METH)-seeking relapse is associated with memory and synaptic plasticity changes. Serotonin is a key neuromodulator in this process. While there is a known distribution of 5-HT 1D receptors in reward and memory areas, such as the hippocampus, its physiological function is currently unknown. Here, we evaluated effect of a 5-HT 1D receptor agonist, PNU142633, on the reinstatement of METH-seeking behavior and long-term potentiation. Rats were implanted with a cannula into lateral ventricle, then treated with saline or METH (5 mg/kg) during the acquisition phase of the conditioned place preference (CPP) test. On day 13 of the extinction phase, METH groups were divided into four groups: METH (0: saline, 1, or 2.5 (priming METH) mg/ kg; i.p.) + vehicle (5 µl/rat) or a priming dose of METH (2.5 mg/kg; i.p.) + PNU (2 µg/5 µl; i.c.v.) and their preference scores were calculated on reinstatement day (day 14). Immediately following this, electrophysiology was performed to assay the field excitatory postsynaptic potential (fEPSP) slope and population spike (PS) amplitude between groups. The results showed that CPP induction by METH gradually declined to extinction on days 12 and 13. A priming METH treatment significantly increased preference for the METH-paired chamber when compared with other groups, but pre-treatment with PNU significantly attenuated this effect. PS amplitude and fEPSP slopes in vehicle + priming METH rats were greater when compared with other groups. Furthermore, PNU attenuated the priming METH-induced increase in PS amplitude. These findings suggest that PNU can decrease synaptic transmission and prevent METH reinstatement in rats.
Pharmacology Biochemistry and Behavior, 1991
BILSKY, E. J. AND L. D. REID. MDL72222, a serotonin 5-HT3 receptor antagonist, blocks MDMA's abili.ty to establish a conditioned place preference. PHARMACOL BIOCHEM BEHAV 39(2) 509-512, 1991.-Methylenedioxymethamphetamine (MDMA) has previously been shown to produce a positive conditioned place preference (CPP) among rats. Here the effects of doses of a specific 5-HT3 antagonist, MDL72222, on MDMA's ability to produce a CPP were assessed. A dose of MDL72222 (0.03 rog/kg) blocked the establishment of a MDMA CPP. These results support the suggestions that compounds affecting the 5-HT3 receptor may be of particular interest in studying the pharmacology of self-administered drugs.
A B S T R A C T Relapse following a prolonged period of drug cessation is a key barrier in the treatment of methamphetamine (METH) addiction, for which pharmacological treatment exhibits little efficacy. Previous studies have suggested that this process involves alterations in levels of serotonin (5-HT) in the brain. Although the 5-HT 1F receptor has been implicated in the reward pathway, its physiological functions remain unknown. In the present study, we examined the effect of the 5-HT 1F agonist LY 344864 on the reinstatement of METH-seeking behavior in rats using a conditioned place preference (CPP) paradigm. The CPP paradigm was first used to determine the effective doses of LY and METH. Four groups were then conditioned with METH (5 mg/kg; i.p.), while the sham group received saline. METH-induced CPP was subsequently extinguished. On the 13th day of extinction, the rats received either METH (0, 1, or 2.5 mg/kg; i.p.) plus vehicle or priming METH plus LY (2 μg/5 μL; i.c.v.). On reinstatement day, preference scores were calculated as the difference in time spent in the drug-paired and vehicle-paired compartments. Rats conditioned with the lowest effective dose of METH (5 mg/kg) exhibited significant differences in pre-and post-testing preference scores. Preference scores were significantly higher in the saline + METH group than in the control group. Furthermore, preference scores were significantly higher in rats that had received priming METH treatment, and pre-treatment with LY significantly attenuated the re-instatement of METH-seeking behavior. These findings suggest that future studies should evaluate the therapeutic potential of 5-HT 1F agonists for preventing relapse in individuals with METH addiction.
Psychopharmacology, 1986
Place preferences induced by the indirect dopamine (DA) receptor agonists amphetamine (AMP) and methylphenidate (MPD) were investigated using an unbiased compartment procedure. In this procedure, prior to drug conditioning, rats did not exhibit preferences for either of the two compartments in a shuttle box. Both stimulants produced place preferences. Repeated testing of the MPD conditioned animals revealed an extinction-like decrease in preferences, suggesting that place preferences produced by MPD result from conditioning of MPD's reinforcing properties to environmental cues. During conditioning, the DA receptor antagonist haloperidol was administered prior to drug (S +) treatments, or prior to both drug and vehicle (S-) treatments. Haloperidol pretreatment blocked place preferences induced by AMP but not by MPD. In contrast, haloperidol blocked locomotor activity stimulated by either AMP or MPD. These results suggest that the reinforcing properties of MPD and AMP may be mediated by different mechanisms, while the locomotor stimulant effects of the two drugs have common neural substrates.