Conditioned Place Preference Task Research Articles

T275. Going Wireless: Validation of a Novel Neurostimulation Technology in a Conditioned Place Preference Task

Deep brain stimulation (DBS) technologies have attracted increasing interest in the treatment of psychiatric disease due to growing evidence of disrupted brain circuits and connectivity in several psychopathologies. Animal models of DBS would be helpful, but to mimic human DBS, those stimulators should not require bulky, limiting tethers. We aimed to validate a novel wireless neurostimulator device, the e-Particle (EP), using rewarding medial forebrain bundle (MFB) stimulation in a conditioned place preference (CPP) paradigm.

Adolescent THC exposure does not sensitize conditioned place preferences to subthreshold d-amphetamine in male and female rats.

The acute effects of marijuana consumption on brain physiology and behaviour are well documented, but the long-term effects of its chronic use are less well known. Chronic marijuana use during adolescence is of increased interest, given that the majority of individuals first use marijuana during this developmental stage , and adolescent marijuana use is thought to increase the susceptibility to abusing other drugs when exposed later in life. It is possible that marijuana use during critical periods in adolescence could lead to increased sensitivity to other drugs of abuse later on. To test this, we chronically administered ∆ 9-tetrahydrocannabinol (THC) to male and female Long-Evans (LER) and Wistar (WR) rats directly after puberty onset. Rats matured to postnatal day 90 before being exposed to a conditioned place preference task (CPP). A subthreshold dose of d-amphetamine, found not to induce place preference in drug naïve rats, was used as the unconditioned stimulus. The effect of d-amphetamine on neural activity was inferred by quantifying cfos expression in the nucleus accumbens and dorsal hippocampus following CPP training. Chronic exposure to THC post-puberty had no potentiating effect on a subthreshold dose of d-amphetamine to induce CPP. No differences in cfos expression were observed. These results show that chronic exposure to THC during puberty did not increase sensitivity to d-amphetamine in adult LER and WR rats. This supports the concept that THC may not sensitize the response to all drugs of abuse.

Evaluation of the rewarding properties of nicotine and caffeine by implementation of a five-choice conditioned place preference task in zebrafish

The rewarding properties of drugs in zebrafish can be studied using the conditioned place preference (CPP) paradigm. Most devices that have been used for CPP consist of two-half tanks with or without a central chamber. Here we evaluated the rewarding effects of nicotine and caffeine using a tank with five arms distributed radially from a central chamber that we have denoted Fish Tank Radial Maze (FTRM). Zebrafish were trained to associate nicotine or caffeine with a coloured arm. In testing sessions to assess CPP induction, between two and five different arms were available to explore. We found that when offering the two arms, one of them associated to the drug mediating conditioning for 14 days, zebrafish showed nicotine-induced CPP but not caffeine-induced CPP. When zebrafish had the option to explore drug-paired arms together with new coloured arms as putative distractors, the nicotine-CPP strength was maintained for at least three days. The presence of novel environments induced caffeine-CPP, which was still positive after three days of testing sessions. Complementary behavioural data supported these findings. Nicotine-CPP was prevented by the histone deacetylase inhibitor phenylbutyrate administered during conditioning; however, there were no effects on caffeine-CPP. The specific acetylation of lysine 9 in histone 3 (H3-K9) was increased in nicotine-conditioned zebrafish brains. This study suggests that novel environmental cues facilitate drug-environment associations, and hence, the use of drugs of abuse.

Conditioned place preference training prevents hippocampal depotentiation in an orexin-dependent manner

BackgroundLong-term potentiation (LTP) is well recognized as a cellular-correlated synaptic plasticity of learning and memory. However, its reversal forms of synaptic plasticity, depotentiation, is less studied and its association with behaviors is also far from clear. Previously, we have shown that nanomolar orexin A can prevent the depotentiation induced by low frequency stimulation (LFS) following theta burst stimulation-induced LTP, namely inducing re-potentiation, at hippocampal CA1 synapses in vitro. Here, we explored the functional correlate of this orexin-mediated hippocampal re-potentiation.Methods and resultsWe found that intraperitoneal (i.p.) injection process-paired contextual exposures during the conditioned place preference (CPP) task in mice resulted in re-potentiation at CA1 synapses of hippocampal slices, regardless of whether the CPP behavior is expressed or not. Simply exposing the mouse in the CPP apparatus, or giving the mouse consecutive i.p. injections of saline in its home cage or a novel cage did not lead to hippocampal re-potentiation. Besides, this CPP training process-induced hippocampal re-potentiation was prevented when mice were pretreated with TCS1102, a dual orexin receptor antagonist. These results suggest that the expression of hippocampal re-potentiation is orexin-dependent and requires the association of differential spatial contexts and i.p. injections in the CPP apparatus.ConclusionsTogether, we reveal an unprecedentedly orexin-mediated modulation on hippocampal depotentiation by the training process in the CPP paradigm.

MicroRNA expression signature of methamphetamine use and addiction in the rat nucleus accumbens.

Methamphetamine (METH) is a highly addictive psycho-stimulant that induces behavioral changes due to high level of METH-induced dopamine in the brain. Nucleus accumbens (NAc) plays an important role in these changes, especially in drug addiction. However, little is known about the underlying molecular mechanisms of METH-induced addiction. The objective of this study was to establish a behavioral model of METH use and addiction using escalating doses of METH over 15days and to determine the global miRNA expression profiling in NAc of METH-addicted rats. In the behavioral study, the experimental rats were divided into 3 groups of 9 each: a control group, a single dose METH (5mg/kg) treatment group and a continuous 15 alternate days METH (0.25, 0.5, 1, 2, 3, 4, 5mg/kg) treatment group. Following that, six rats in each group were randomly selected for global miRNA profiling. Addiction behavior in rats was established using Conditioned Place Preference task. The analysis of the miRNA profiling in the NAc was performed using Affymetric microarray GeneChip® System. The findings indicated that a continuous 15 alternate days METH treatment rats showed a preference for the drug-paired compartment of the CPP. However, a one-time acute treatment with 5mg/kg METH did not show any significant difference in preference when compared with controls. Differential profiling of miRNAs indicated that 166 miRNAs were up-regulated and 4 down-regulated in the chronic METH-treatment group when compared to controls. In comparing the chronic treatment group with the acute treatment group, 52 miRNAs were shown to be up-regulated and 7 were down-regulated. MiRNAs including miR-496-3p, miR-194-5p, miR-200b-3p and miR-181a-5p, were found to be significantly associated with METH addiction. Canonical pathway analysis revealed that a high number of METH addiction-related miRNAs play important roles in the MAPK, CREB, G-Protein Couple Receptor and GnRH Signaling pathways. Our results suggest that dynamic changes occur in the expression of miRNAs following METH exposure and addiction.

Prenatal chlorpyrifos leads to autism-like deficits in C57Bl6/J mice

BackgroundChildren are at daily risk for exposure to organophosphate insecticides, of which the most common is chlorpyrifos (CPF). Exposure of pregnant women to CPF was linked to decreased birth weight, abnormal reflexes, reduction in IQ, as well as increased maternal reports of signs of pervasive developmental disorder. The aim of current study was to examine the long term effects of prenatal exposure to CPF in C57BL/6 J (B6) mice with specific focus on social and repetitive behavior.MethodsB6 female mice were treated with vehicle, 2.5 mg/kg CPF or 5 mg/kg of CPF on gestational days 12–15 by oral gavage. On postnatal days (PND’s) 6–12 early development and neuromotor ability were assessed by measuring 3 neonatal reflexes in the offspring. In adulthood, PND 90, social behavior was investigated using the social preference, social novelty and social conditioned place preference tasks. Object recognition and restricted interest, measured by the repetitive novel object contact task (RNOC), were also assessed on PN D 90. In order to rule out the possibility that CPF administration induced alterations in maternal care, the dams’ behavior was evaluated via the maternal retrieval task.ResultsCPF treatment resulted in delayed development of neonatal reflexes on PND’s 6–12. On PND 90, mice treated prenatally with the 5.0 mg/kg dose exhibited reduced preference towards an unfamiliar conspecific in the social preference test and reduced social conditioned place preference. In the RNOC task, mice exposed prenatally to 2.5 mg/kg dose of CPF showed enhanced restricted interest. CPF administration did not impair dams’ behavior and did not cause memory or recognition deficit as was observed in the object recognition task.ConclusionsOur data indicate that gestational exposure to CPF has long-term deleterious effects on social behavior and limits exploration of novel objects.

Virtual reality conditioned place preference using monetary reward

Computerized tasks based on conditioned place preference (CPP) methodology offer the opportunity to study learning mechanisms involved in conditioned reward in humans. In this study, we examined acquisition and extinction of a CPP for virtual environments associated with monetary reward ($).Healthy men and women (N=57) completed a computerized CPP task in which they controlled an avatar within a virtual environment. On day 1, subjects completed 6 conditioning trials in which one room was paired with high $ and another with low $. Acquisition of place conditioning was assessed by measuring the time spent in each room during an exploration test of the virtual environments and using self-reported ratings of room liking and preference. Twenty-four hours later, retention and extinction of CPP were assessed during 4 successive exploration tests of the virtual environments.Participants exhibited a place preference for (spent significantly more time in) the virtual room paired with high $ over the one paired with low $ (p=0.015). They also reported that they preferred the high $ room (p<0.001) and liked it significantly more than the low $ room (p<0.001). However, these preferences were short-lived: 24h later subjects did not exhibit a behavioral or subjective preference for the high $ room.These findings show that individuals exhibit transient behavioral and subjective preferences for a virtual environment paired with monetary reward. Variations on this task may be useful to study mechanisms and brain substrates involved in conditioned reward and to examine the influence of drugs upon appetitive conditioning.

The Personality Trait of Intolerance to Uncertainty Affects Behavior in a Novel Computer-Based Conditioned Place Preference Task.

Recent work has found that personality factors that confer vulnerability to addiction can also affect learning and economic decision making. One personality trait which has been implicated in vulnerability to addiction is intolerance to uncertainty (IU), i.e., a preference for familiar over unknown (possibly better) options. In animals, the motivation to obtain drugs is often assessed through conditioned place preference (CPP), which compares preference for contexts where drug reward was previously received. It is an open question whether participants with high IU also show heightened preference for previously rewarded contexts. To address this question, we developed a novel computer-based CPP task for humans in which participants guide an avatar through a paradigm in which one room contains frequent reward (i.e., rich) and one contains less frequent reward (i.e., poor). Following exposure to both contexts, subjects are assessed for preference to enter the previously rich and previously poor room. Individuals with low IU showed little bias to enter the previously rich room first, and instead entered both rooms at about the same rate which may indicate a foraging behavior. By contrast, those with high IU showed a strong bias to enter the previously rich room first. This suggests an increased tendency to chase reward in the intolerant group, consistent with previously observed behavior in opioid-addicted individuals. Thus, the personality factor of high IU may produce a pre-existing cognitive bias that provides a mechanism to promote decision-making processes that increase vulnerability to addiction.

Abuse potential of methylenedioxymethamphetamine (MDMA) and its derivatives in zebrafish: role of serotonin 5HT2-type receptors.

The synthetic phenethylamines are recreational drugs known to produce psychostimulant effects. However, their abuse potential has not been widely studied. Here, we investigated the rewarding and the hallucinatory effects of 2,5-dimetoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine (PMA) in comparison with the classical 3,4-methylenedioxymethamphetamine (MDMA). In addition, the role of serotonin 5-HT2-like receptor on the abovementioned effects was evaluated. Zebrafish were intramuscularly (i.m.) treated with a wide range of doses of DOB (0.1-20mg/kg), PMA (0.0005-2mg/kg), or MDMA (0.5-160mg/kg). Animals were submitted to a conditioned place preference (CPP) task, to investigation of the rewarding properties, and to the evaluation of hallucinatory behavior in terms of appearance of a trance-like behavior. The serotonin 5-HT2 subtype receptor antagonist ritanserin (0.025-2.5mg/kg) in association with the maximal effective dose of MDMA, DOB, and PMA was given i.m., and the effect on CPP or hallucinatory behavior was evaluated. MDMA and its derivatives exhibited CPP in a biphasic fashion, being PMA the most potent. This effect was accompanied, for DOB (2mg/kg) and PMA (0.1mg/kg), by a trance-like hallucinatory behavior. MDMA at a high dose as 160mg/kg did not induce any hallucinatory behavior. Ritanserin significantly blocked the rewarding and hallucinatory effects suggesting the involvement of serotonin 5HT2 subtype receptor. Collectively, these findings demonstrate for the first time that the rewarding properties of DOB and PMA are accompanied by hallucinatory behavior through a serotonergic system and reinforce zebrafish as an emerging experimental model for screening new hallucinogens.

A role for the endocannabinoid 2-arachidonoyl-sn-glycerol for social and high-fat food reward in male mice.

The endocannabinoid system is an important modulator of brain reward signaling. Investigations have focused on cannabinoid (CB1) receptors, because dissection of specific contributions of individual endocannabinoids has been limited by the available toolset. While we recently described an important role for the endocannabinoid anandamide in the regulation of social reward, it remains to be determined whether the other major endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG), serves a similar or different function. To study the role of 2-AG in natural reward, we used a transgenic mouse model (MGL-Tg mice) in which forebrain 2-AG levels are selectively reduced. We complemented behavioral analysis with measurements of brain 2-AG levels. We tested male MGL-Tg mice in conditioned place preference (CPP) tasks for high-fat food, social contact, and cocaine. We measured 2-AG content in the brain regions of interest by liquid chromatography/mass spectrometry. Male MGL-Tg mice are impaired in developing CPP for high-fat food and social interaction, but do develop CPP for cocaine. Furthermore, compared to isolated mice, levels of 2-AG in socially stimulated wild-type mice are higher in the nucleus accumbens and ventral hippocampus (183 and 140% of controls, respectively), but unchanged in the medial prefrontal cortex. The results suggest that reducing 2-AG-mediated endocannabinoid signaling impairs social and high-fat food reward in male mice, and that social stimulation mobilizes 2-AG in key brain regions implicated in the control of motivated behavior. The time course of this response differentiates 2-AG from anandamide, whose role in mediating social reward was previously documented.

Seeking behavior, place conditioning, and resistance to conditioned suppression of feeding in rats intermittently exposed to palatable food.

Binge eating disorder is characterized by excessive consumption of highly palatable food within short periods of time accompanied by loss of control over eating. Extensive evidence provides support for the consideration of binge eating disorder as an addiction-like disorder. In this study, we wanted to determine whether rats undergoing an operant binge-like eating procedure could develop maladaptive forms of conditioned feeding behaviors. For this purpose, we trained male rats to self-administer either a sugary, highly palatable diet ("Palatable" rats) or a chow diet ("Chow" rats) for 1 hour a day. After escalation and stabilization of palatable food intake, we tested Chow and Palatable rats in (a) a conditioned place preference test, (b) a second-order schedule of reinforcement, (c) a cue-induced suppression of feeding test. In the conditioned place preference task, Palatable rats spent significantly more time in the compartment that was previously paired with the palatable food, compared to Chow controls. Furthermore, in the second-order schedule of reinforcement task, Palatable rats exhibited active lever responding 4- to 6-fold higher than Chow control rats. Finally, in the cue-induced suppression of feeding test, although Chow control subjects reduced responding by 32% in the presence of the conditioned punishment, Palatable rats persevered in responding despite the aversive cue. These results further characterize this animal model of binge-like eating and provide additional evidence for the addictive properties of highly palatable food.

Part III: Principal component analysis: bridging the gap between strain, sex and drug effects

Previous work has identified the adolescent period as particularly sensitive to the short- and long-term effects of marijuana and its main psychoactive component Δ9-tetrahydrocannabinol (THC). However, other studies have identified certain backgrounds as more sensitive than others, including the sex of the individual or the strain of the rat used. Further, the effects of THC may be specific to certain behavioural tasks (e.g. measures of anxiety), and the consequences of THC are not seen equally across all behavioural measures. Here, data obtained from adolescent male and female Long-Evans and Wistar rats exposed to THC and tested as adults, which, using standard ANOVA testing, showed strain- and sex-specific effects of THC, was analyzed using principal component analysis (PCA). PCA allowed for the examination of the relative contribution of our variables of interest to the variance in the data obtained from multiple behavioural tasks, including the skilled reaching task, the Morris water task, the discriminative fear-conditioning to context task, the elevated plus maze task and the conditioned place preference task to a low dose of amphetamine, as well as volumetric estimates of brain volumes and cfos activation. We observed that early life experience accounted for a large proportion of variance across data sets, although its relative contribution varied across tasks. Additionally, THC accounted for a very small proportion of the variance across all behavioural tasks. We demonstrate here that by using PCA, we were able to describe the main variables of interest and demonstrate that THC exposure had a negligible effect on the variance in the data set.

High versus low fat/sugar food affects the behavioral, but not the cortisol response of marmoset monkeys in a conditioned-place-preference task

The effect of a high (chocolate) versus low fat/sugar (chow) food on a conditioned-place-preference (CPP) task was evaluated in marmoset monkeys. Anxiety-related behaviors and cortisol levels before and after the CPP task were also measured. Subjects were habituated to a two-compartment CPP box and then, on alternate days, had access to only one compartment during daily 15-min conditionings, for a total of 14 trials. Marmosets were provisioned with chocolate chips in the CC-paired compartment on odd-numbered trials and standard chow in the CW-paired compartment on even-numbered trials. They were then tested for preferring the CC-paired context after a 24-h interval. During the conditioning, a significantly greater amount (in kcal/trial) of chocolate was consumed than chow, yet the foraging pattern of both food types was similar. On the test trial, the time spent in the CC-paired context increased significantly compared to pre-CPP levels, yet this response was not readily predicted by baseline behavioral or cortisol levels. Also, the chocolate CPP response was positively correlated with foraging time, rather than the amount of calories consumed. The sudden absence of the food increased exploration, while the chocolate CPP effect was associated with vigilance — both anxiety-related behaviors in marmosets. This behavioral profile occurred regardless of any concomitant change or correlation with cortisol. Therefore, the high fat/sugar food was more prone to be overly consumed by the marmosets, to induce a CPP response and to lead to anxiety-related behavior in its absence.

Conditioned place preferences in humans using virtual reality

To extend a standard paradigm of conditioning in nonhumans to humans, we created a virtual reality (VR) conditioned place preference task, with real-life food rewards. Undergraduates were placed into a VR environment consisting of 2 visually distinct rooms. On Day 1, participants underwent 6 pairing sessions in which they were confined into one of the two rooms and explored the VR environment. Room A was paired with real-life M&Ms for 3 sessions, and Room B was paired with no food for 3 sessions. Day 2 was the test day, administered the next day, and participants were given free access to the entire VR environment for 5min. In experiment 1, participants were food restricted, and we observed that on the test day, participants display a significant conditioned place preference for the VR room previously paired with food (p<0.001). Additionally, they display a significant explicit preference for the M&M-paired room in a forced-choice of "Which room do you like best?". In experiment 2, when participants were not food restricted, there was no evidence of a place preference, either implicitly (e.g. dwell time) or explicitly. Hence, we show that we can reliably establish a place preference in humans, but that the preference is contingent on the participants' hunger state. Future research will examine the extent to which these preferences can be blocked or extinguished as well as whether these preferences are evident using other reinforcers.

Time-of-day effect on a food-induced conditioned place preference task in monkeys

Time can be an important contextual cue for cognitive performance, with implications for reward-associated learned behaviors such as (drug and food) addiction. So, we analyzed: (1) if marmoset monkeys develop a place preference that is conditioned to previous pairings with a highly-palatable food reward; (2) if the response is strongest when training and testing times match – time stamp effect; and (3) if there is an optimal time of the day (morning vs. afternoon) when this preference occurs – time-of-day effect. Subjects were first habituated to a two-compartment conditioned-place-preference (CPP) box. Then, during six training sessions held either in the morning or afternoon, a mixture of jellybeans and live mealworms was made available in a specific compartment. Marmosets were subsequently tested for preferring the food-paired context at the circadian time that either matched or was different from that of training. Compared to baseline levels, only subjects trained and tested in the afternoon made significantly longer and more frequent visits to the food-paired context and with a shorter latency to first entry. Thus, highly-palatable food rewards induced a CPP response. This behavior was exhibited only when training and testing times overlapped and during a restricted circadian timeframe (afternoon), consistent with a time-stamp and time-of-day effect, respectively. In this case, time may have been an internal circadian contextual cue. Whether due to circadian-mediated oscillations in memory and/or reward processes, such findings may be applied to addiction and other learned behaviors.

Role of dorsal hippocampal orexin-1 receptors in associating morphine reward with contextual stimuli

In this study, we evaluated the role of orexin receptors in the dorsal hippocampus (dHPC) in the development of morphine-induced conditioned place preference (CPP) and modification of hippocampal c-Fos and cyclic AMP response element-binding protein (CREB) levels. Orexin-A (0.5, 5, and 50 pmol) and the orexin-1 receptor antagonist, SB334867 (10, 20, and 40 nmol), were bilaterally infused into the dHPC immediately before conditioning with morphine (0.5 or 7.5 mg/kg) using the CPP task. Western blotting was then used to measure the protein levels of c-Fos, total CREB, and phosphorylated CREB (pCREB) in the hippocampus. Orexin did not enhance the rewarding efficacy of morphine (0.5 mg/kg), but caused a reduction in hippocampal c-Fos. Successful conditioning with morphine (7.5 mg/kg) was associated with increased levels of hippocampal c-Fos and CREB, but with decreased CREB phosphorylation. Intrahippocampal administration of SB334867 before conditioning sessions disrupted the rewarding effect of morphine (7.5 mg/kg) and blocked morphine-induced increases in hippocampal CREB protein levels. The results suggest that orexin signaling within the dHPC is necessary for the development of morphine CPP. Morphine reward is related to altered levels of hippocampal c-Fos and CREB. Inhibition of morphine-induced increases in CREB levels might be the underlying mechanism for the disruption of morphine CPP.

Roles of levo-tetrahydropalmatine in modulating methamphetamine reward behavior

Levo-tetrahydropalmatine (l-THP), as an alkaloid purified from the traditional Chinese herbal medicine Corydalis and Stephania, has been widely used to produce many traditional Chinese herbal preparations. The effect of l-THP on methamphetamine-induced reward learning still remains unclear although it has been proved to be effective on treating allodynia and drug addiction. This experiment has been designed to examine the effect of l-THP on the acquisition, expression, extinction, and reinstatement of methamphetamine-induced conditioned place preference (CPP) in mice. The results show that methamphetamine (METH) could induce CPP in mice at doses of 0.5mg/kg, 1.0mg/kg and 2.0mg/kg respectively, but l-THP alone could not do so. Meanwhile, l-THP could not induce conditioned place aversion at doses of 1.25mg/kg to 20.0mg/kg in mice, but it could attenuate the acquisition and expression of METH-induced CPP and facilitate the extinction of METH-induced CPP in mice. Besides, l-THP could inhibit the reinstatement of METH-induced CPP at the dose of 10.0mg/kg whether it was given in the extinction training phase or 30min before the reinstatement. These results suggest that l-THP can globally suppress the rewarding properties of METH on all phases of the CPP task and it may have potential effects on the treatment of METH abuse.

Inducing "cravings" in humans using a virtual reality conditioned place preference task

Inducing "cravings" in humans using a virtual reality conditioned place preference task

Multiple effects of circadian dysfunction induced by photoperiod shifts: Alterations in context memory and food metabolism in the same subjects

Humans exposed to shiftwork conditions have been reported to have increased susceptibility to various health problems including various forms of dementia, cancer, heart disease, and metabolic disorders related to obesity. The present experiments assessed the effects of circadian disruption on learning and memory function and various food related processes including diet consumption rates, food metabolism, and changes in body weight. These experiments utilized a novel variant of the conditioned place preference task (CPP) that is normally used to assess Pavlovian associative learning and memory processes produced via repeated context-reward pairings. For the present experiments, the standard CPP paradigm was modified in that both contexts were paired with food, but the dietary constituents of the food were different. In particular, we were interested in whether rats could differentiate between two types of carbohydrates, simple (dextrose) and complex (starch). Consumption rates for each type of carbohydrate were measured throughout training. A test of context preference without the food present was also conducted. At the end of behavioral testing, a fasting glucose test and a glucose challenge test were administered. Chronic photoperiod shifting resulted in impaired context learning and memory processes thought to be mediated by a neural circuit centered on the hippocampus. The results also showed that preferences for the different carbohydrate diets were altered in rats experiencing photoperiod shifting in that they maintained an initial preference for the simple carbohydrate throughout training. Lastly, photoperiod shifting resulted in changes in fasting blood glucose levels and elicited weight gain. These results show that chronic photoperiod shifting, which likely resulted in circadian dysfunction, impairs multiple functions of the brain and/or body in the same individual.

Conditioned place preference induced by electrical stimulation of the insular cortex: effects of naloxone

The insular cortex has been related to various sensory, regulatory, and learning processes, which frequently include affective-emotional components. The objective of this study was to investigate the possibility of inducing reinforcing effects by electrical stimulation of this cortical region in Wistar rats. Concurrent conditioned place preference tasks were conducted for this purpose, using two rectangular mazes that differed in dimensions, texture, and spatial orientation. A significant correlation was found in the preferences induced by insular cortex electrical stimulation between the two mazes. Animals showed consistent preference or avoidance behaviors associated with simultaneous insular cortex stimulation. No electrical self-stimulation was achieved. In a second experiment, animals that showed consistent place preference after the simultaneous insular cortex electrical stimulation were administered with 4 mg/ml/kg of naloxone. The results revealed that this opiate antagonist blocked concurrent place preference learning when the task was conducted in a new maze but not when it was conducted in the same maze as that in which the animals had learned the task. These results are discussed in terms of the participation of the insular cortex in various reward and aversion modalities.