Conditioned Place Preference Box Research Articles

Effect of risperidone on morphine-induced conditioned place preference and dopamine receptor D2 gene expression in male rat hippocampus.

Previous studies suggest the possible effect of risperidone on brain reward system and D1 and D2 dopamine receptors' involvement in morphine-induced conditioned place preference (CPP). The present study was designed to investigate the effect of risperidone as an atypical antipsychotic drug on morphine-induced CPP and D2-like dopamine receptor gene expression in rat. An unbiased CPP paradigm was used to study the effect of risperidone. Intraperitoneal (i.p.) injection of risperidone (1, 2, and 4mg/kg) was performed 30min before the morphine (10mg/kg, i.p.) injection and just after the rat was placed in the CPP box. The open field test was used to assay the locomotor activity of animal. The gene expression of D2 dopamine receptor in hippocampus was measured by real-time PCR technique. The hippocampi of rats were also used for histology evaluation. Morphine-produced (10mg/kg) CPP and morphine-induced CPP were reversed only by the administration of a low dose of risperidone (1mg/kg). Low dose of risperidone (1mg/kg) showed no effect on locomotor activity but a higher dose of risperidone (2 and 4mg/kg) decreased locomotor activity. Real-time PCR data analysis revealed that the gene expression of D2 dopamine receptor had significant difference between morphine and a 1mg/kg dose of risperidone. Moreover, in histological evaluation, apoptosis was observed in the morphine group, whereas there was no evidence of apoptosis in the risperidone-treated groups. Our results suggest that risperidone (1mg/kg) reverses the morphine-induced CPP and may reduce the rewarding properties of morphine. It is also demonstrated that risperidone decreases the expression of D2 receptor in rat hippocampus. Therefore, risperidone can be considered potential adjunct therapy in morphine dependence.

A morphine reward generalization mouse model based on conditioned place preference and aversion.

Conditioned place preference (CPP) is a common behavioral paradigm for studying the association of unconditioned stimulus reward memory with context. Generalization is a flexiblememory recall pattern developedon thebasis oforiginal memory. Drug-seeking behaviors in substance usedisorders(SUDs) exhibit diversity,which wegenerallyattribute to the highly generalizedfeaturesof SUD memory. However, to date, there are no animal models for SUD generalization studies. We design the generalization box (G-box) and the generalization retrieval process based on the conditioned place preference (CPP) model. In the memory retrieval stage, we replaced the conditioning CPP box (T-box) with a generalization box (G-box) to study drug generalization memory. For appearance, the generalized boxes have different angles and numbers of sides compared to the conditioning boxes. For the visual cues, the shapes of the symbols are different (triangle icons for the hexagonal chamber and dot icons for the round chamber), but the orientation information remains the same. To establish CPP generalization, the mice received morphine on the vertical or horizontal side of a conditioning box (T-box) andsaline on theotherside. Then, after CPP conditioning, the generalization test was performed in a generalization box (G-box: hexagonal chamber and Gr-box: round chamber) 21 days later. CPP-conditioned mice still displayed a clear preference for similar visual information in the G-box. CPA-conditioned mice behaved similarly to CPP, with mice consistently avoiding similar visual information in the G-box. We further observed that the generalization results are similar using two generalization boxes (G-box and Gr-box). In this study, we succeeded in creating a simple and effective generalization model for morphine reward. The establishment of this model provides a new tool for generalization studies of SUD and therapy in humans.

Examination of neuroinflammatory cytokine interleukin-1 beta expression in the medial prefrontal cortex, amygdala, and hippocampus for the paradoxical effects of reward and aversion induced by morphine

A growing body of evidence has shown that abused drugs could simultaneously induce the paradoxical effect-reward and aversion. Moreover, the medial prefrontal cortex (mPFC), amygdala, and hippocampus were involved in this paradoxical effect by abused drugs. However, no research examined whether neuroinflammatory changes in the mPFC [including cingulate cortex area 1 (Cg1); prelimbic cortex (PrL); infralimbic cortex (IL)], basolateral amygdala, and hippocampus [e.g., CA1, CA2, CA3, and dentate gyrus (DG)] after morphine-induced reward in conditioned place preference (CPP) and aversion in conditioned taste aversion (CTA). The results showed that after morphine administration, the consumption of a 0.1% saccharin solution decreased; the mean time spent in the morphine-paired side compartment of the CPP box increased, indicating that morphine simultaneously induced the paradoxical effects of reward and aversion. The PrL and IL of the mPFC, the BLA of the amygdala, the CA1, CA2, CA3, and DG of the hippocampus but not the Cg1 presented hyperactive IL-1β expression in response to morphine's aversion and reward. The mPFC, amygdala, and hippocampus may appear neuroinflammation activity following morphine-induced paradoxical effect-reward in CPP and aversion in CTA. The present data may provide a better understanding of the relationship between neuroinflammation and morphine addiction.

Drug-Seeking Behavior Is Significantly Attenuated in Nutritionally Supplemented Cocaine Withdrawn Sprague-Dawley Rats

Aim: The effect of patented nutritional supplementation on drug-seeking behavior in cocaine addicted rats during acute drug withdrawal was investigated using a biased Conditioned Place Preference (CPP) paradigm. Method: Twenty-four (24) male Sprague-Dawley rats with pre-conditioned preference for the black chamber of the CPP box were randomly divided into Cocaine (COC) or Saline (SAL) treated groups. Rats (n = 12) treated with cocaine hydrochloride 20 mg/kg/ml, i.p. (COC group) were confined individually to the white chamber on days 1, 3, 5 and 7. On alternate days, they were given 1 ml saline vehicle, i.p. and confined to the black chamber. Control rats (SAL group, n = 12) received only vehicle on all 8 days and were confined on alternate days to the white or black chamber. Positive place preference was confirmed for COC rats, which subsequently received 6 increasing daily doses of cocaine. CPP performances of both COC and SAL rats were recorded following an acute 3-day withdrawal period. All animals were then randomly assigned to rats fed either chow reconstituted with the nutritional supplement (COC-S and SAL-S) or standard rat chow (COC-N and SAL-N) for 8 weeks, followed by final CPP performances. Results: Following supplementation, COC-S rats made significantly less entries and time spent in the white chamber (p Conclusion: Drug-seeking behavior that persisted during cocaine withdrawal was significantly diminished in the nutritionally supplemented.

Low-cost conditioned place preference setup including video recording and analysis of behaviour

The conditioned place preference (CPP) paradigm is widely used in rodent research to test the rewarding and aversive properties of different stimuli. Despite its relative simplicity, commercially available CPP systems are often costly. Here we describe the construction of a CPP setup and a behavioral data analysis pipeline incorporating:• a CPP box which can be built in a single day by using widely available and affordable materials.• an open source computer system for data acquisition (based on Raspberry Pi).• a freely available behavioural analysis software.The behavioural analysis allows for measurement of both locomotor activity and time spent in a zone of interest. Including all components, our setup costs ~1/10 of the cost of the least expensive commercially available CPP boxes alone (not including data acquisition and analysis). We validated the setup by showing that a 4 mg/kg dose of amphetamine increases locomotor activity acutely in adolescent male mice and induces conditioned preference for the drug-paired compartment in the CPP test.

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats.

A major cause of repeated relapses is a craving for the drug. Drug craving increases progressively during the abstinence period, a phenomenon termed incubation of drug craving. Here, we describe a morphine conditioned place preference (CPP) protocol for measuring the incubation of craving in rats. In this protocol, a CPP paradigm mainly employing somatosensory cues is used to establish a long-term reward memory of morphine. A three-chamber CPP box that differs in the texture of the chamber floor is constructed. First, the animals are tested for their baseline preference to the two side chambers for three consecutive days. Then, they are injected intraperitoneally with morphine/saline and put into their non-preferred/preferred chamber for 45 min. After 6 days of conditioning, their preference to the side chambers is tested for 15 min at different time points after the last conditioning session. With this paradigm, the reward memory of morphine could last for at least 18 days. To test whether the above-mentioned protocol can model increased craving, the number of entrances into the two side chambers are counted during the abstinence period. The results show that the entrances increased, suggesting that the CPP paradigm could mimic the incubation of craving. Future studies can employ this model to study neural mechanisms underlying long-term memory and incubation of craving.

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats

A major cause of repeated relapses is a craving for the drug. Drug craving increases progressively during the abstinence period, a phenomenon termed incubation of drug craving. Here, we describe a morphine conditioned place preference (CPP) protocol for measuring the incubation of craving in rats. In this protocol, a CPP paradigm mainly employing somatosensory cues is used to establish a long-term reward memory of morphine. A three-chamber CPP box that differs in the texture of the chamber floor is constructed. First, the animals are tested for their baseline preference to the two side chambers for three consecutive days. Then, they are injected intraperitoneally with morphine/saline and put into their non-preferred/preferred chamber for 45 min. After 6 days of conditioning, their preference to the side chambers is tested for 15 min at different time points after the last conditioning session. With this paradigm, the reward memory of morphine could last for at least 18 days. To test whether the above-mentioned protocol can model increased craving, the number of entrances into the two side chambers are counted during the abstinence period. The results show that the entrances increased, suggesting that the CPP paradigm could mimic the incubation of craving. Future studies can employ this model to study neural mechanisms underlying long-term memory and incubation of craving.

Glucocorticoid receptors in the basolateral amygdala mediated the restraint stress-induced reinstatement of methamphetamine-seeking behaviors in rats

Methamphetamine (METH) addiction is a growing epidemic worldwide. It is a common psychiatric disease and stress has an important role in the drug seeking and relapse behaviors. The involvement of the basolateral amygdala (BLA) in effects of stress on the reward pathway has been discussed in several studies. In this study, we tried to find out the involvement of glucocorticoid receptors (GRs) in the BLA in stress-induced reinstatement of the extinguished METH-induced conditioned place preference (CPP) in rats. The CPP paradigm was done in eighty-one adult male Wistar rats weighing 220–250 g. The animals received a daily injection of methamphetamine (0.5 mg/kg), during the conditioning phase. In extinction phase, the rats were put in the CPP box for 30 min per day for 8 days. After the extinction, the animals were exposed to acute restraint stress (ARS), 3 h before subcutaneous administration of sub-threshold dose of methamphetamine (0.125 mg/kg), based on our previous study, in reinstatement phase. In separated groups, the rats were exposed to chronic restraint stress (CRS) for 1 h each day during the extinction phase. To block the GRs in BLA, the animals unilaterally received RU38486 as GRs antagonist (10, 30 and 90 ng/0.3 μl DMSO) in all ARS groups on reinstatement day. In separated experiments, RU38486 (3, 10 and 30 ng/0.3 μl DMSO) was microinjected into the BLA in CRS groups prior to exposure to stress every day in extinction phase. The results revealed that intra-BLA RU38486 in ARS (90 ng) and CRS (10 and 30 ng) groups significantly prevented the stress-induced reinstatement. It can be proposed that stress partially exerts its effect on the reward pathway via GRs in the BLA. This effect was not quite similar in acute and chronic stress conditions.

Effects of Acute and Chronic Restraint Stress on Reinstatement of Extinguished Methamphetamine-induced Conditioned Place Preference in Rats

Introduction:Methamphetamine (METH) is a neurotoxic psychostimulant with highly addictive potential that leads to compulsive drug use and vulnerability to relapse. Environmental cues, such as drug exposure, peer influence, and social stress, are the powerful triggers of drug relapse. In this study, we tried to find out the effect of acute and chronic restraint stress on reinstatement of extinguished METH-induced Conditioned Place Preference (CPP) in rats.Methods:Subcutaneous (SC) administration of METH (0.125, 0.25, 0.5, 1, 2 and 4 mg/kg) could induce CPP and it was found that METH with the dose of 0.5 mg/kg was more potent than other doses. In extinction phase, rats were put in the CPP box for 30 min per day for 8 consecutive days. After extinction, animals were exposed to restraint stress (3-h period, as an acute stress) 60 min before subcutaneous administration of ineffective dose of METH (0.125 mg/kg) in order to reinstate the extinguished METH-induced CPP. For induction of the chronic stress during extinction phase, the animals were exposed to the restraint stress for one hour per day.Results:The results showed that the effective dose of METH to induce CPP was 0.5 mg/kg. Based on the results, physical stress (restraint stress) whether acute and chronic, can significantly induce reinstatement of METH-induced CPP (P˂0.001) in extinguished animals.Conclusion:Additionally, the chronic restraint stress could reduce duration of extinction (maintenance) of METH-induced CPP. It seems that exposure to the stress induces the relapse in abstinent amphetamine, but acute and chronic situation have a different reaction.

Effect of reward alteration following acupuncture for morphine withdrawal rats on neuronal discharges in the ventral medial prefrontal cortex

To observe the effect of reward alteration following acupuncture for morphine withdrawal rats on the behavior and neuronal discharges in the medial prefrontal cortex (mPFC). The Sprague-Dawley (SD) rats were randomly allocated into a model group, a confinement group, an electroacupuncture (EA) group, and a control group. Rats with morphine addiction were made by intraperitoneal injection of naloxone (same dose injection of saline for rats in the control group), followed by a 2-week morphine withdrawal. Acupuncture and confinement were completed during the morphine withdrawal period. Upon withdrawal, the rats received conditioned place preference (CPP) training and open field test. The multi-channel neural signal processor was used in the electrophysiological experiment to measure the neuronal discharges in different subareas of prefrontal cortex in CPP box and aversion box. Rats in the model group and the confinement group spent longer period of time in CPP box than those in the EA group and the control group (all P<0.01); there was no statistically significant difference between the EA group and the control group. The total distances of movement by rats in the model group and the confinement group were longer than those in the EA group and the control group (all P<0.01). The mPFC neuronal discharge frequencies were compared between morphine preference box and aversion box. The mPFC neuronal discharge frequencies in the model group and the confinement group were higher than those in the EA group and the control group (all P<0.05); there was no statistically significant difference between the EA group and the control group. Acupuncture can effectively interfere with the reward alteration following morphine withdrawal, possibly because of its involvement with the mPFC neuronal discharges.

Monosodium glutamate-associated alterations in open field, anxiety-related and conditioned place preference behaviours in mice.

The present study investigated changes in behaviour associated with oral monosodium glutamate (a flavouring agent), using the open field, elevated plus maze and conditioned place preference (CPP) paradigms, respectively. Mice were assigned to two groups for CPP [monosodium glutamate (MSG)-naïve (n=40) and MSG-pretreated (n=40)] and two groups for open field (OF) and elevated plus maze (EPM) tests [n=40 each], respectively. Animals in respective groups were then divided into four subgroups (n=10) (vehicle or MSG (80, 160 and 320mg/kg)). MSG-naïve mice were observed in the CPP box in three phases (pre-conditioning, conditioning and post-conditioning). Mice were conditioned to MSG or an equivalent volume of saline. The MSG pretreatment group received vehicle or respective doses of MSG daily for 21days, prior to conditioning. Mice in the OF or EPM groups received vehicle or doses of MSG (orally) for 21days, at 10ml/kg. Open field or EPM behaviours were assessed on days 1 and 21. At the end of the experiments, mice in the OF groups were sacrificed and brain homogenates used to assay glutamate and glutamine. Results showed that administration of MSG was associated with a decrease in rearing, dose-related mixed horizontal locomotor, grooming and anxiety-related response and an increase in brain glutamate/glutamine levels. Following exposure to the CPP paradigm, MSG-naïve and MSG-pretreated mice both showed 'drug-paired' chamber preference. The study concluded that MSG (at the administered doses) was associated with changes in open field activities, anxiety-related behaviours and brain glutamate/glutamine levels; its ingestion also probably leads to a stimulation of the brain reward system.

Drug Seeking Behavior of Amphetamine Addicted Sprague-Dawley Rats Is Eliminated after Nutritional Supplementation

Aim: The effectiveness of nutritional supplementation on drug-seeking behavior of amphetamine-addicted rats during withdrawal was investigated using a biased conditioned place preference (CPP) paradigm. Method: Twenty-four male Sprague-Dawley rats exhibiting baseline preference for the black chamber during a 20-minute pre-conditioning exploration of the CPP box completed the study. On alternate days of an 8-day schedule, twelve rats (Group AMP) were randomly selected, given either amphetamine sulfate (5 mg/ml, i.p.) and confined to the white chamber; or vehicle (1 ml saline, i.p.) and confined to the black chamber. A significant increased percentage time spent and number of entries made by Group AMP to the drug-paired, white chamber on the test day confirmed amphetamine addiction. Group AMP subsequently received increasing doses of amphetamine over 6 days. Following acute drug withdrawal, their CPP performance was compared with that of vehicle treated rats (Group SAL). Groups AMP and SAL were equally divided and randomly assigned to animals fed chow reconstituted with the nutritional supplement (AMP-S and SAL-S) over 8 weeks or standard rat chow (AMP-N and SAL-N). CPP performances for all rats were determined blindly from video recordings following this period. Results: Nutritionally supplemented, amphetamine withdrawn rats (AMP-S) exhibited significantly decreased percentage entries and time spent in the white chamber (p < 0.05), indicating preference for the black chamber and diminished drug-seeking behavior. ANOVA revealed that after 8 weeks of dietary supplementation, AMP-S rats behaved like drug-na?ve, control animals. Conclusion: Drug-seeking behavior by amphetamine-addicted animals was eliminated after treatment with a nutritionally supplemented diet.

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.

Consumption of a highly palatable food induces a lasting place-conditioning memory in marmoset monkeys

Highly palatible foods may induce addiction-related behaviors. However, this has yet to be established in non-human primates. Therefore, we evaluated whether marmoset monkeys (Calllithrix penicillata) acquire a conditioned-place-preference (CPP) for chocolate and if this response is detectable after a 24-h and 15-day period. Subjects were first habituated to a two-compartment CPP box and then randomly assigned to a chocolate or control group. Thereafter, they were given access to only one compartment during daily 15-min conditionings, held on six consecutive days. On each trial, the chocolate group received pieces of chocolate (50g) in this context, whereas controls were not given a food reward. Marmosets were subsequently tested for preferring this (food) paired context after a 24-h and 15-day interval. During conditioning, individual foraging and the amount of chocolate ingested by each pair of the chocolate group remained constant. However, compared to pre-CPP levels, the time spent inside/in contact with the conditioned compartment increased significantly, while the latency to first entry decreased on both post-CPP intervals. For controls, the parameters remained unaltered. Thus, chocolate induced a persistent CPP response—an aspect usually associated with drug-related rewards.

Forced swim stress but not exogenous corticosterone could induce the reinstatement of extinguished morphine conditioned place preference in rats: Involvement of glucocorticoid receptors in the basolateral amygdala

Addiction is a common psychiatric disease and stress has an important role in the drug seeking and relapse behaviors. The involvement of basolateral amygdala (BLA) in the effects of stress on reward pathway is discussed in several studies. In this study, we tried to find out the involvement of glucocorticoid receptors (GRs) in the BLA in stress-induced reinstatement of extinguished morphine-induced conditioned place preference (CPP) in rats. The CPP paradigm was done in adult male Wistar rats weighing 220–320g, and conditioning score and locomotor activity were recorded by Ethovision software. Animals received effective dose of morphine (5mg/kg) daily, during the 3-day conditioning phase. In extinction phase, rats were put in the CPP box for 30min a day for 8 days. After extinction, animals were injected by corticosterone (10m/kg) or exposed to forced swim stress (FSS) 10min before subcutaneous administration of ineffective dose of morphine (0.5mg/kg) in order to reinstate the extinguished morphine-CPP. To block the glucocorticoid receptors in the BLA, after stereotaxic surgery and placing two cannulae in this area bilaterally, animals received GR antagonist mifepristone (RU38486; 0.3, 3 and 30ng/0.3μl DMSO per side) prior to exposure to FSS then each animal received ineffective dose of morphine (0.5mg/kg) as drug-induced reinstatement. The results revealed that physical stress (FSS) but not exogenous corticosterone can significantly induce reinstatement of extinguished morphine-CPP, and intra-BLA mifepristone prevents the stress-induced reinstatement. It can be proposed that stress partially exerts its effect on the reward pathway via glucocorticoid receptors in the BLA.

Sexual experience blocks the ability of clitoral stimulation to induce a conditioned place preference in the rat

We have previously established the rewarding value of clitoral stimulation (CLS) through the demonstration that manual, distributed, CLS induces a significant conditioned place preference (CPP) and conditioned partner preference in naïve, hormonally primed and non-hormonally primed rats. The present experiment asks whether previous sexual experience might inhibit the ability of clitoral stimulation to induce a conditioned place preference.Female Long–Evans rats were ovariectomized and treated with 10μg of estradiol benzoate (EB) 48h and 500μg of progesterone (P) 4h prior to receiving either 0, 1, or 5 consecutive copulatory sessions with a sexually vigorous male. Each copulatory session ended when females received at least 1 ejaculation. Females then experienced 10 alternating trials of distributed CLS or no CLS paired with one side of a non-biased CPP box under the same hormone-priming regimen. Females that experienced 5 consecutive copulatory sessions did not develop a significant place preference indicated by both a preference score (the proportion of time spent in the reinforced chamber) and a difference score (time in the non-reinforced chamber minus the time in the reinforced chamber) compared prior to and following the 10 conditioning trials. This suggests that repeated copulatory experience might induce a desensitization of the genitosensory circuit since copulation includes both clitoral, and vaginocervical stimulation from mounts plus intromissions. Alternatively, repeated sexual experience prior to conditioning may generate a UCS pre-exposure effect that cannot be altered when manual clitoral stimulation is paired with a new environment.

Injection of colchicine in intra-hippocampal cortical area 1 enhances novelty seeking behavior

Objective:Colchicine, a potent neurotoxin derived of plant has been recently identified as a degenerative toxin of small pyramidal cells in the hippocampal cortical area 1 (CA1). In this study, the effect of the alkaloid intra hippocampal CA1 on the novelty seeking behavior in the conditioning task was measured.Materials and Methods:Injections of colchicine (1-75 μg/rat, intra-CA1) were performed in cannulated male Wistar rats while being settled in the stereotaxic apparatus. Control group was solely injected saline (1 μl/rat, intra-CA1). One week later, after recovery, all the animals passed the novelty seeking paradigm using an unbiased conditioning task. They were habituated with the conditioned place preference (CPP) apparatus on day 1. Then they were confined in one part of the CPP box for 3 more days. Finally, the animals were tested in the last day. To evaluate, the possible cell injury effect of the toxin on the pyramidal cells of the CA1 both the motivational staying signal in the parts of the box and the non-motivational locomotive signs of the rats were measured.Results:Based on the present study, the alkaloid caused significant novelty seeking behavior at higher doses. It also affected the compartment entering behavior in the colchicine received group. However, the alkaloid did not show the significant effect on sniffing, rearing or grooming in the rats.Conclusion:Injection of colchicine intra-CA1 may impair the neuronal transmission of motivational information by the pyramidal cells in the dorsal hippocampus.

Clitoral stimulation induces conditioned place preference and Fos activation in the rat

The present study examined the ability of clitoral stimulation (CLS) to induce conditioned place preference (CPP) and Fos protein in the brain. Ovariectomized, hormone-primed Long–Evans rats were randomly assigned to receive either distributed CLS (1 stimulation every 5 s for 1 min prior to being placed in one distinctive side of a nonbiased CPP box for 2 min, after which the cycle of stimulation and CPP exposure were repeated for 4 more cycles, totaling 60 stimulations) or continuous CLS (1 stimulation per second for 1 min with 2 min in one side of the CPP box, repeated for 4 more cycles, totaling 300 stimulations). Two days later, females were placed into the other side of the CPP box without prior stimulation. CPP was tested after 5 sequential exposures each of CLS and no stimulation. Females given distributed stimulation developed a significant CPP whereas females given continuous stimulation did not. CLS induced Fos in hypothalamic and limbic structures, including the nucleus accumbens, piriform cortex, arcuate nucleus, and dorsomedial portion of the ventromedial hypothalamus, compared to no stimulation. However, distributed CLS induced more Fos in the medial preoptic area than continuous CLS or no stimulation. In contrast, continuous CLS induced more Fos in the posteroventral medial amygdala compared to no stimulation. These data indicate that CLS induces a reward state in the rat and a pattern of Fos activation in regions of the brain that process genitosensory input, incentive salience, and reward.

Sexual reward in male rats: Effects of sexual experience on conditioned place preferences associated with ejaculation and intromissions

Various behavioral models and studies have provided evidence suggesting that male rat sexual behavior has rewarding and reinforcing properties. However, there is little information regarding the rewarding values of the different components of sexual behavior. Therefore, this study used a conditioned place preference (CPP) paradigm to address whether ejaculation and intromissions differ in their rewarding incentive values. We also addressed whether the differential rewarding values were dependent on prior sexual experience. Sexually naïve and experienced males received one pairing of either intromissions or ejaculation with one of the chambers in the CPP box. The amount of time spent in each chamber of the CPP apparatus after conditioning was then measured. Both sexually naïve and sexually experienced males formed a CPP for ejaculation, while only sexually naïve, and not sexually experienced, males formed a CPP for intromissions. Moreover, in sexually naïve males, multiple pairings of ejaculation with the designated chamber resulted in a CPP relative to the control chamber paired with display of intromissions. These data support the hypothesis that there is a hierarchy of rewarding sexual behavior, with ejaculation being the most rewarding component, and that the rewarding incentive value of other components of sexual behavior is dependent upon prior sexual experience.

Effects of buspirone on the immediate positive and delayed negative properties of intravenous cocaine as measured in the conditioned place preference test

In prior work, we have demonstrated that the behavioral effects of cocaine adhere to the predictions of the opponent-process theory of drug action. Animals develop conditioned place preferences for distinct locations paired with the immediate effects of IV cocaine, but learn to avoid places paired with the effects present 15-min post-injection. It was of interest to assess the putative role of 5-HT in producing the negative properties of cocaine since cocaine acts to inhibit the reuptake of serotonin (5-HT) and since such actions have been associated with anxiogenic consequences. Male rats were administered a reinforcing dose of cocaine (1.0 mg/kg IV) and then placed – either immediately or after a 15-min delay – into one side of a two-compartment (black–white) conditioned place preference (CPP) box for 5-min. On alternate days, the animals received IV saline injections and were placed in the opposite side of the CPP box. This continued for eight days after which animals had experienced 4 pairings of cocaine with one side (black or white) of the CPP apparatus, and 4 saline pairings with the opposite side. Other groups of rats were treated identically except that 30-min prior to placement into the apparatus, these animals received an IP injection of saline or buspirone (a partial 5-HT 1A agonist) at a dose that we have shown to be anxiolytic (2.5 mg/kg IP). Control animals experienced either buspirone or saline pretreatments without cocaine. Our results confirm that animals increase the time spent on the side paired with the immediate effects of cocaine (compared to baseline), but tend to avoid the side paired with effects present 15-min post-injection. Buspirone had no effect on the immediate rewarding properties of cocaine, but completely reversed the negative properties present 15-min post-cocaine. These results are consistent with the view that attenuation of 5-HT neurotransmission (via the autoreceptor agonist properties of buspirone) can reverse the negative impact of IV cocaine.