Place Preference Model Research Articles

A place preference test in the fish Nile tilapia

The Nile tilapia fish ( Oreochromis niloticus) has a high potential to be used as a model in neuroscience studies. In the present study, the preference of the Nile tilapia between a gravel-enriched (GEE), a shelter-enriched (SEE) or a non-enriched (NEE) environment was determined, for developing a place preference model. Nile tilapia had an initial preference for GEE, but after 1 day of observation, the fish stabilized their frequency of visits among compartments. Hence, any stimulus motivating tilapia increase in compartment visiting indicates a positively reinforcing effect. This feature is very useful for the development of new behavioural paradigms for fish in tests using environmental discrimination, such as the conditioning place preference test.

Dorsal, but not ventral, hippocampal lesions disrupt cocaine place conditioning.

The environment in which cocaine is experienced becomes associated with the effects of the drug and can then elicit cocaine craving. This study examined whether the hippocampus is involved in such associations using the conditioned place preference model. Rats received bilateral lesions of the dorsal or ventral hippocampus and were then conditioned to associate a particular environment with cocaine. Following conditioning, rats with lesions of the dorsal, but not ventral, hippocampus failed to demonstrate conditioned place preference for the cocaine-associated environment. These findings suggest that the dorsal hippocampus plays a role in the association of environmental stimuli with the effects of cocaine and may have important implications for understanding craving elicited by cocaine-conditioned stimuli.

Effects of β-funaltrexamine and naloxonazine on single-trial morphine-conditioned place preference and locomotor activity

The current study assessed the ability of the selective irreversible μ-opioid receptor antagonists β-funaltrexamine (βFNA) and naloxonazine (NALZ) to alter the locomotor and rewarding effects of a single intravenous injection of morphine using the conditioned place preference (CPP) model. In the first experiment, rats were conditioned with a single injection of morphine (10 mg/kg iv) paired with one compartment of a CPP apparatus and then were tested for CPP at either 1 or 7 days after conditioning. Rats showed hypoactivity following acute morphine on the conditioning trial and showed CPP when tested either 1 or 7 days later. In the next experiments, rats were pretreated with βFNA (20 mg/kg sc, 20 h before conditioning), NALZ (15 or 30 mg/kg sc, 24 h before conditioning) or saline and then were conditioned with a single injection of morphine (10 mg/kg iv) or saline. Pretreatment with NALZ alone, but not βFNA, significantly decreased locomotor activity; neither antagonist alone produced a significant shift in preference for either compartment of the CPP apparatus. Pretreatment with either βFNA or NALZ blocked completely morphine-induced hypoactivity, but neither antagonist had a significant effect on morphine CPP. These results indicate that μ-opioid receptors are more critically involved in acute morphine-induced hypoactivity than in acute morphine reward.

Analysis of the effects of CPA and l-histidine on goldfish tested on a conditioned place preference model

The aim of this study was to investigate whether the histamine H 1- receptor blocker chlorpheniramine (CPA) and the histaminergic precursor l-histidine have reinforcing effects in goldfish ( Carassius auratus). We used a place-preference procedure in a four-compartment aquarium in which, on the first day, the animals were placed for 30 min for habituation. On the second day, the time spent in each chamber was recorded for 10 min in order to determine which was preferred. After 24 h a non-transparent acrylic division was placed in the aquarium to make four identical compartments. The fish were injected intraperotoneally (i.p.) with l-histidine in three doses: 100, 250, and 500 mg/kg of body-weight ( n=20) and with vehicle control ( n=20). After 30 min the animals were placed in the intermediate preference chamber for another 30 min. The CPA was injected i.p in four doses; 0.4, 1.0, 4.0 or 8.0 mg/kg ( n=16) or vehicle ( n=16) and after 5 min the animals were placed in the intermediate preference chamber for another 30 min. On the fourth day the procedure of the second day was repeated. The results indicate that the group treated with 500 mg/kg l-histidine spent significantly more time in the paired compartment when compared with the time spent before treatment (Wilcoxon Signed Rank Test, P=0.0172). The same behavior was not observed in other treatment groups ( P>0.05). The results indicate a reinforcing effect of l-histidine in this place preference model with goldfish.

Effect of tetrandrine on morphine induced hyperactivity and reinforcement in mice

After single administration of morphine and the motion activity was measured by ambulometer, conditioned place-preference paradigm was used to study the reinforcing effect of morphine, climbing behavior was used to evaluate the relation with Dopaminergic system and immediate early expression of c-fos gene was in brain was showed by immunohistochemical method. Single administration of morphine could induce hyperactivity, repeated treatment would produce a conditioned place-preference response, tetrandrine 30 or 60 mg/kg hypodermic injection could inhibit the morphine induced hyperactivity, 60 mg/kg could inhibit the conditioned place-preference response but no influence on climbing behavior in mice was found. Tetrandrine could inhibit the c-fos gene expression in nucleus accumbens, ventral tegmental and prefrontal cortex in place-preference model formed by morphine. Tetrandrine could inhibit the hyperactivity and conditioned place preference response induced by morphine, it might relate to reducing the c-fos gene expression in special area of brain in mice.

Effect of acute and chronic stress restraint on amphetamine-associated place preference: involvement of dopamine D 1 and D 2 receptors

The purpose of this study was to determine the d-amphetamine (1.0, 1.5 and 2 mg/kg i.p.)-induced place preference in rats pre-exposed to acute or chronic restraint stress, using the conditioned place preference model. We also studied the involvement of opioid and dopamine mechanisms in the acute restraint stress-induced increase of d-amphetamine-induced place preference. A single restraint session (2 h) but not chronic restraint (2 h/day for 7 days) leading to adaptation to the stressor, enhanced the d-amphetamine-induced place preference. This enhancing effect was prevented by haloperidol administration (0.4 mg/kg i.p.), (±)-sulpiride (60 mg/kg i.p.) or R(+)-SCH-23390 hydrochloride ( R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine hydrochloride, 30 μg/kg i.p.) 10–20 min prior to the acute restraint session. However, naltrexone pretreatment (1 or 2 mg/kg i.p.) failed to prevent the acute restraint-induced enhancement of d-amphetamine-induced place preference. These results suggest that: (1) the enhancement of d-amphetamine-induced place preference occurred after a single restraint stress but not following chronic restraint stress, (2) the stimulation of both dopamine D 1 and D 2 receptors is necessary for the development of single restraint stress-induced enhancement of d-amphetamine-induced place preference and (3) apparently, an opioid system is not involved in this acute restraint-induced effect.

Phentermine and Fenfluramine: Preclinical Studies in Animal Models of Cocaine Addiction.

Combined dopamine (DA) and 5-hydroxytryptamine (5-HT) releasers such as phentermine (PHEN) and fenfluramine (FEN) are reported, in open label studies, to reduce craving for alcohol and cocaine and to prevent relapse. The objective of the studies reported here was to assess the actions of these agents alone and in combination in various animal models of drug addiction. Study 1. in vivo microdialysis experiments demonstrate that these agents preferentially release mesolimbic DA (PHEN) and 5-HT (FEN). Patients who relapse and use cocaine while taking these medications report diminished cocaine-like subjective effects. Microdialysis experiments were performed in awake rats, and dialysate samples were analyzed for DA and 5-HT. PHEN (1 mg/kg, intravenously (i.v.)) elevated DA (2-3-fold) for over 1.5 hr. Administration of cocaine (3 mg/kg, i.v.) increased DA 6-fold in saline-treated rats, but only 3-fold in PHEN-treated rats. PHEN did not reduce cocaine-induced increases in 5-HT. Study 2. These agents were assessed in a mouse model of cocaine-conditioned motoric activity (CCMA). Pretreatment with non-activating doses of PHEN (4.6 mg/kg, intraperitoneally (i.p.)) enhanced CCMA, whereas non-depressing doses of FEN (0.1 mg/kg, i.p.) did not alter CCMA or the PHEN-induced increase in CCMA. In contrast, sub-effective doses of FEN reduced CCMA stereotypy-like locomotion, whereas sub-effective doses of PHEN were without effect. PHEN reversed the FEN-induced increase in CCMA stereotypy-like locomotion. Study 3. PHEN and FEN were assessed in the conditioned place preference model. FEN produced marked aversions for an environment previously associated with its administration and the minimum dose producing this effect was 3.0 mg/kg. In contrast, administration of PHEN, amphetamine (1.0-3.0 mg/kg) or morphine (3.0-5.0 mg/kg) produced dose-related preferences for the drug-paired place. However, the magnitude of the response to PHEN was less than that produced by the other prototypic drugs of abuse. In rats that received FEN (0.3 or 3.0 mg/kg) in combination with PHEN (3.0 mg/kg), the conditioned rewarding effects of PHEN were abolished. These data demonstrate that the rewarding effects of PHEN can be conditioned to stimuli previously associated with its administration. However, the conditioned response to this agent is less then that produced by prototypic drugs of abuse. The finding that PHEN-induced place preferences were attenuated by doses of FEN demonstrates that the combination of FEN/PHEN is devoid of motivational effects. The preclinical data obtained with PHEN/FEN in various models of drug provide a strong rationale for pursuing controlled clinical trials in humans with agents that act via a similar mechanism of action.

The influence of physical and temporal characteristics on the pattern of mouse preference behaviour in the pre-conditioning phase of a place preference model

The influence of physical and temporal characteristics on the pattern of mouse preference behaviour in the pre-conditioning phase of a place preference model

Repeated testing attenuates conditioned place preference with cocaine.

Cocaine-treated rats acquired a preference for cocaine-associated contextual stimuli (CS) relative to saline-injected control rats. However, when animals were given repeated tests for conditioned place preference intermittent between conditioning trials, they displayed an attenuation in strength of conditioning. This attenuation was not due to pharmacologic tolerance (Experiment 1), but rather reflected a disruption in learning due to exposure to the CS alone (Experiment 2). Like other examples of classical conditioning, the strength of the conditioned response (CR) as assessed by the conditioned place preference model may be influenced by partial reinforcement.