Conditioned Place Preference Chamber Research Articles

The Abnormalities in Event-Related Oscillations in Patients With Dementia During Recognition of Emotional Facial Expressions

Attention deficit/hyperactivity disorder (ADHD) is a risk factor for tobacco use and dependence. This study examines the responsiveness to nicotine of an adolescent model of ADHD, the spontaneously hypertensive rat (SHR). The conditioned place preference (CPP) procedure was used to assess nicotine-induced locomotion and conditioned reward in SHR and the Wistar Kyoto (WKY) control strain over a range of nicotine doses (0.0, 0.1, 0.3 and 0.6 mg/kg). Prior to conditioning, SHRs were more active and less biased toward one side of the CPP chamber than WKY rats. Following conditioning, SHRs developed CPP to the highest dose of nicotine (0.6 mg/kg), whereas WKYs did not develop CPP to any nicotine dose tested. During conditioning, SHRs displayed greater locomotor activity in the nicotine-paired compartment than in the saline-paired compartment across conditioning trials. SHRs that received nicotine (0.1, 0.3, 0.6 mg/kg) in the nicotine-paired compartment showed an increase in locomotor activity between conditioning trials. Nicotine did not significantly affect WKY locomotor activity. These findings suggest that the SHR strain is a suitable model for studying ADHD-related nicotine use and dependence, but highlights potential limitations of the WKY control strain and the CPP procedure for modeling ADHD-related nicotine reward.

Δ<sup>9</sup>-Tetrahydrocannabinol Produced Positive Place Preference in Mice without Significant <i>Ex-Vivo</i> Effect on Hepatic Arylamine N-Acetyltransferase Activity: Implications for Its Addictive Liability and Absence of Effect on Xenobiotic Metabolism

Aim: Δ9-Tetrahydrocannabinol (Δ9-THC) is a potentially addictive cannabinoid. Its impact on the activity of liver arylamine N-Acetyltransferase (NAT) has not been reported. This study investigated the rewarding effects of Δ9-THC in mice and whether Δ9-THC had any impact ex-vivo and in-vitro on NAT activity. Methods: Thirty-six Swiss albinomice randomly assigned to six groups (n = 6) completed a biased, 8-week Conditioned Place Preference (CPP) paradigm. Mice exhibiting ~80% preference for the black chamber at pre-conditioning were selected. Treatment groups were administered Δ9-THC (0.10, 0.50 or 2.0 mg/kg/mL, ip) or amphetamine (AMP, 5.0 mg/kg/mL, ip); while untreated groups (controls) received vehicle solutions (coconut oil or 0.9% saline). Entries and time spent in the white, drug-paired chamber during a 15-min post-conditioning exploration of the CPP apparatus were compared with the pre-conditioning exploratory scores. Livers from Δ9-THC treated and untreated mice were excised and NAT enzyme activity determined ex-vivo using a spectrophotometric assay with p-anisidine as substrate. The impact of varying concentrations of Δ9-THC (0.00 - 162 μM) on the activities of NAT from untreated mice livers were also investigated in-vitro. Results: Δ9-THC treated mice entered and spent significantly more time in the drug-paired CPP chamber (p ≤ 0.05) at post-conditioning vs pre-conditioning (F = 11.22). Mice treated with 2.0 mg/kg Δ9-THC made significantly more entries into the drug-paired chamber (p ≤ 0.05) as compared with their vehicle controls. AMP-treated mice displayed significant (p In-vitro NAT evaluations revealed a dose-dependent inhibitory impact of Δ9-THC on NAT activity with an IC50 value of 34.97 ±1.58 μM. Ex-vivo evaluations of livers from Δ9-THC treated mice showed no significant impact on liver NAT enzyme activity. Conclusion: Δ9-THC induced significant conditioned place preference (drug reward) and produced a moderate dose-dependent inhibition on NAT activity in-vitro, but not ex-vivo.

Differential behavioral effects of ethanol pre-exposure in male and female zebrafish (Danio rerio)

Alcohol exposure in adolescence is a contributing factor toward reward-seeking behavior in adulthood. This reward-seeking behavior is assessed in animal models using the conditioned place preference (CPP) paradigm. In this study, ethanol-induced change in time spent by zebrafish on the initially non-preferred tank side was studied by conditioning adult zebrafish to ethanol dissolved in water (0.00% 1.00%; 1.25%; 1.50%; 1.60%; 1.75% vol/vol) paired with an initially non-preferred environment. Following a single conditioning cycle, fish swam unrestricted in the CPP chamber to assess changes in preference. Daily 20-min pre-exposure to ethanol for 1 week during the juvenile stage starting at either 20days post fertilization (dpf) or 40 dpf altered percent time spent on the ethanol-paired side in adulthood in a dose-dependent and sex-dependent manner. The results suggest that male and female zebrafish are an effective model in which to investigate behavioral correlates of ethanol-induced changes in neural circuits implicated in reward and anxiety.

EFFECTS OF MAGNESIUM SULFATE ON THE ACQUISITION AND REINSTATEMENT OF MORPHINE-INDUCED CONDITIONED PLACE PREFERENCE IN MICE

Relapse to opioid, even long time after withdrawal, is one of the most important problems of opiate withdrawal programs. Magnesium has been shown that; inhibit glutamate release and induces N-Methyl-D-aspartate (NMDA) antagonistic effects; moreover, glutamate NMDA antagonists contribute to the reinforcement of morphine. In the current study, the effects of magnesium sulfate on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP) in an animal model were investigated. The acquisition and extinction and reinstatement phases induced using morphine 40 and 10mg/kg. Magnesium sulfate 300 and 600 mg/kg (not 150mg/kg) reduced morphine dependence. Additionally, tendency of animals to the white compartment of CPP chamber significantly decreased. Magnesium sulfate inhibits morphine tendency and reinstatement probably via NMDA antagonistic effects. Keywords : magnesium sulfate; morphine; conditioned place preference.

Neurochemical and behavioural indices of exercise reward are independent of exercise controllability.

Brain reward circuits are implicated in stress-related psychiatric disorders. Exercise reduces the incidence of stress-related disorders, but the contribution of exercise reward to stress resistance is unknown. Exercise-induced stress resistance is independent of exercise controllability; both voluntary running (VR) and forced running (FR) protect rats against the anxiety-like and depression-like behavioural consequences of stress. Voluntary exercise is a natural reward, but whether rats find FR rewarding is unknown. Moreover, the contribution of dopamine (DA) and striatal reward circuits to exercise reward is not well characterized. Adult, male rats were assigned to locked wheels, VR, or FR groups. FR rats were forced to run in a pattern resembling the natural wheel running behavior of rats. Both VR and FR increased the reward-related plasticity marker ΔFosB in the dorsal striatum and nucleus accumbens, and increased the activity of DA neurons in the lateral ventral tegmental area, as revealed by immunohistochemistry for tyrosine hydroxylase and pCREB. Both VR and FR rats developed conditioned place preference (CPP) to the side of a CPP chamber paired with exercise. Re-exposure to the exercise-paired side of the CPP chamber elicited conditioned increases in cfos mRNA in direct-pathway (dynorphin-positive) neurons in the dorsal striatum and nucleus accumbens in both VR and FR rats, and in tyrosine hydroxylase-positive neurons in the lateral ventral tegmental area of VR rats only. The results suggest that the rewarding effects of exercise are independent of exercise controllability and provide insight into the DA and striatal circuitries involved in exercise reward and exercise-induced stress resistance.

GABAB receptor system modulates mitragynine-induced conditioned place preference in rats

Event Abstract Back to Event GABAB receptor system modulates mitragynine-induced conditioned place preference in rats Nurul H. Mohammad Yusoff1*, Sharif M. Mansor1, Navaratnam Visweswaran1, Christian P. Muller2 and Zurina Hassan1* 1 Universiti Sains Malaysia, Centre for Drug Research, Malaysia 2 Friedrich-Alexander-University Erlangen-Nuremberg, Department of Psychiatry and Psychotherapy, Germany Many drugs of abuse produce rewarding effects, as evidenced by their ability to induce conditioned place preference (CPP). Mitragynine, the major active alkaloid of Mitragyna speciosa (Kratom) plant, has been reported to possess this response in animal model. Considering the role of GABAB receptor subtypes in mediating the rewarding properties of various classes of addictive drugs, the present study aims to examine the involvement of GABAB receptor system on acquisition and expression of mitragynine-induced CPP. An unbiased 3-chamber CPP paradigm was employed, which consisted of 3 phases; pre-conditioning (2 days), conditioning (8 days), and CPP test. Pre-conditioning test was performed to assess initial individual preference for each CPP chamber. Groups of rats were conditioned with mitragynine (10 mg/kg), combination of mitragynine and baclofen (1.25, 2.5 and 5.0 mg/kg) or vehicle paired with a distinctive chamber. On alternating days, rats were given vehicle and paired with another distinctive chamber. After 8 conditioning sessions, a preference (CPP) test was conducted whereby rats had full access to the entire apparatus under the influence of either baclofen (1.25, 2.5 and 5.0 mg/kg) or saline. Mitragynine-conditioned animals showed CPP as demonstrated by an increased amount of time spent in the drug-associated chamber during the CPP test relative to pre-conditioning test. The administration of baclofen (2.5 and 5.0 mg/kg) 30 min prior to mitragynine injection inhibited the acquisition of mitragynine-induced CPP. In addition, the administration of baclofen (2.5 and 5.0 mg/kg) to the mitragynine-conditioned animals 30 min prior to the CPP test blocked the expression of CPP responses. These findings showed that activation of GABAB receptors by baclofen suppressed the acquisition and expression of CPP effects produced by mitragynine. Mitragynine-induced CPP effects are dependent on the activity of GABAB receptor system during acquisition and expression phases. Acknowledgements Financial support was received from Higher Education Centre of Excellence (HiCoE) special funding (304/CDADAH/650527/K134) and FRGS (203/CDADAH/6711469) Keywords: Addiction, GABA, conditioned place preference, in vivo, rewarding effect Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: O03: Postgraduate Travel Awardees Oral Session 3 Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Mohammad Yusoff NH, Mansor SM, Visweswaran N, Muller CP and Hassan Z (2016). GABAB receptor system modulates mitragynine-induced conditioned place preference in rats. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00090 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Ms. Nurul H Mohammad Yusoff, Universiti Sains Malaysia, Centre for Drug Research, Minden, Penang, Malaysia, hess_myz@yahoo.com Dr. Zurina Hassan, Universiti Sains Malaysia, Centre for Drug Research, Minden, Penang, Malaysia, zurina_hassan@usm.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Nurul H Mohammad Yusoff Sharif M Mansor Navaratnam Visweswaran Christian P Muller Zurina Hassan Google Nurul H Mohammad Yusoff Sharif M Mansor Navaratnam Visweswaran Christian P Muller Zurina Hassan Google Scholar Nurul H Mohammad Yusoff Sharif M Mansor Navaratnam Visweswaran Christian P Muller Zurina Hassan PubMed Nurul H Mohammad Yusoff Sharif M Mansor Navaratnam Visweswaran Christian P Muller Zurina Hassan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Nicotine-induced place conditioning and locomotor activity in an adolescent animal model of attention deficit/hyperactivity disorder (ADHD)

Attention deficit/hyperactivity disorder (ADHD) is a risk factor for tobacco use and dependence. This study examines the responsiveness to nicotine of an adolescent model of ADHD, the spontaneously hypertensive rat (SHR). The conditioned place preference (CPP) procedure was used to assess nicotine-induced locomotion and conditioned reward in SHR and the Wistar Kyoto (WKY) control strain over a range of nicotine doses (0.0, 0.1, 0.3 and 0.6mg/kg). Prior to conditioning, SHRs were more active and less biased toward one side of the CPP chamber than WKY rats. Following conditioning, SHRs developed CPP to the highest dose of nicotine (0.6mg/kg), whereas WKYs did not develop CPP to any nicotine dose tested. During conditioning, SHRs displayed greater locomotor activity in the nicotine-paired compartment than in the saline-paired compartment across conditioning trials. SHRs that received nicotine (0.1, 0.3, 0.6mg/kg) in the nicotine-paired compartment showed an increase in locomotor activity between conditioning trials. Nicotine did not significantly affect WKY locomotor activity. These findings suggest that the SHR strain is a suitable model for studying ADHD-related nicotine use and dependence, but highlights potential limitations of the WKY control strain and the CPP procedure for modeling ADHD-related nicotine reward.

Congenic dissection of a major QTL for methamphetamine sensitivity implicates epistasis

We previously used the C57BL/6J (B6) × A/J mouse chromosome substitution strain (CSS) panel to identify a major quantitative trait locus (QTL) on chromosome 11 influencing methamphetamine (MA)-induced locomotor activity. We then made an F(2) cross between CSS-11 and B6 and narrowed the locus (Bayes credible interval: 79-109 Mb) which was inherited dominantly and accounted for 14% of the phenotypic variance in the CSS panel. In the present study, we created congenic and subcongenic lines possessing heterozygous portions of this QTL to narrow the interval. We identified one line (84-96 Mb) that recapitulated the QTL, thus narrowing the region to 12 Mb. This interval also produced a small decrease in locomotor activity following prior saline treatment. When we generated subcongenic lines spanning the entire 12-Mb region, the phenotypic difference in MA sensitivity abruptly disappeared, suggesting an epistatic mechanism. We also evaluated the rewarding properties of MA (2 mg/kg, i.p.) in the 84- to 96-Mb congenic line using the conditioned place preference (CPP) test. We replicated the locomotor difference in the MA-paired CPP chamber yet observed no effect of genotype on MA-CPP, supporting the specificity of this QTL for MA-induced locomotor activity under these conditions. Lastly, to aid in prioritizing candidate genes responsible for this QTL, we used the Affymetrix GeneChip(®) Mouse Gene 1.0ST Array to identify genes containing expression QTLs (eQTL) in the striatum of drug-naÏve, congenic mice. These findings highlight the difficulty of using congenic lines to fine map QTLs and illustrate how epistasis may thwart such efforts.

Mice lacking the galanin gene show decreased sensitivity to nicotine conditioned place preference

Previous work has indicated that the neuropeptide galanin decreases sensitivity to the rewarding effects of morphine and cocaine, but increases alcohol drinking. The aim of the current study was to examine the role of galanin signaling in nicotine reward by testing the effects of nicotine in mice lacking galanin peptide (GAL −/−) as compared to wild-type (GAL +/+) controls. Using an unbiased, three-chamber conditioned place preference (CPP) paradigm the dose–response function for nicotine CPP was tested in GAL −/− and GAL +/+ mice. Since activation of extracellular signal-related kinase (ERK2) is involved in the rewarding effects of several classes of drugs of abuse, we then measured the level of ERK2 phosphorylation in the nucleus accumbens shell (NACsh) and core (NACco) of GAL −/− and GAL +/+ mice following re-exposure to the CPP chamber previously paired with nicotine as a marker of mesolimbic system activation. Finally, we examined whether acute nicotine administration affects ERK2 activity in GAL −/− and GAL +/+ mice. GAL −/− mice required a higher dose of nicotine to induce a significant CPP compared to GAL +/+ mice. In the conditioning groups showing significant expression of nicotine CPP, only GAL +/+ mice showed ERK2 activation in the NACsh. This suggests that the nicotine CPP observed in GAL +/+ mice resulted in differential recruitment of ERK signaling in the NACsh compared to GAL −/− mice. In addition, no activation of ERK2 was observed following acute nicotine administration in either genotype. These data, along with prior results, suggest that galanin alters sensitivity to drugs of abuse differentially, with morphine, cocaine and amphetamine place preference suppressed, and nicotine and alcohol preference increased, by galanin signaling.

Augmented cocaine conditioned place preference in rats pretreated with systemic ghrelin

The physiological mechanism through which food restriction (FR) enhances the biobehavioral actions of psychostimulants is unknown but may involve the gut peptide ghrelin. Plasma levels of ghrelin are increased by FR and reduced by eating. Moreover, systemically administered ghrelin crosses into the brain and is known to augment the locomotor-stimulating effects of cocaine [COC: Wellman et al., 2005]. This study sought to determine whether pretreatment with ghrelin (5 nmol) would enhance the rewarding properties of COC (0.0, 0.312, 0.625, or 1.25 mg/kg i.p.) as measured by conditioned place preference (CPP). Adult male Sprague–Dawley rats were given free access to both sides of a CPP chamber to determine initial side preference. The rats were then confined for 30 min to either their preferred side or non-preferred side on 8 consecutive days. When rats were confined to the least preferred side, each was injected with 0.5 ml (i.p.) of either ghrelin (5 nmol) or saline 1 h before the conditioning trial and then injected (i.p.) with one of the COC doses immediately prior to the conditioning trial. On alternate days, rats were injected with vehicle one hour before and again immediately before the conditioning trial. Place preference scores were computed as the differences in time (min) spent on the least preferred side of the chamber for the pre-test and the postconditioning test, covaried by the initial degree of preference (% time spent on the black side during the pre-test). These analyses indicated a significant interaction between ghrelin pretreatment and COC dose on changes in preference scores. Significantly higher place preference scores were noted for rats treated with either 0.312 or 0.625 mg/kg COC doses, but only when these COC doses were preceded by administration of 5 nmol ghrelin. In contrast, saline pretreated rats exhibited significant CPP at the 1.25 mg/kg COC dose, but the ghrelin pretreated group did not. These results provide partial support for the contention that ghrelin pretreatment can augment the rewarding effects of sub-threshold doses of COC in a CPP procedure. Moreover, these findings are consistent with the view that ghrelin may play a role in the capacity of FR to augment psychostimulant action.

Concurrent evaluation of locomotor response to novelty and propensity toward cocaine conditioned place preference in mice

Neural and physiological factors underlying individual differences in the vulnerability to drug abuse are the major questions remained to be determined. The present study described new methods that concurrently assess the relationship between locomotor response to novelty and conditioned place preference (CPP) for cocaine in mice using a novel activity monitor, SCANET. The activity monitor simultaneously measured the distance traveled and the amount of time spent in each side of a two-compartment CPP chamber, and the latency to the first entry into the other side of the CPP chamber. Mice were divided into two groups according to their locomotor response to the first exposure to the CPP chamber during a preconditioning session; high-responder (HR) and low-responder (LR) mice. Following conditioning sessions, the CPP score was shown to be higher in LR mice than in HR mice, especially at low doses of cocaine. In a separate experiment with SCANET, we measured the latency to the first entry into the white-floored compartment from the black-floored compartment of the CPP chamber as an index of anxiety-like behavior. The latency was significantly prolonged in the LR group as compared with the HR group. Thus, the new methods described here are considered to be useful for examining animal models of drug addiction with respect to anxiety-like behavior.

The testosterone metabolite and neurosteroid 3alpha-androstanediol may mediate the effects of testosterone on conditioned place preference.

Testosterone (T) and pregnane neurosteroids can enhance conditioned place preference (CPP). The present experiment examined CPP produced by T and its androgenic metabolite dihydrotestosterone (DHT) and 3alpha-Androstanediol (3alpha-diol; an androstane neurosteroid). Administration of 3alpha-diol (>DHT>T) to intact male Long-Evans rats, 1.0 mg daily for six days, 30 min prior to exposure to the non-preferred side of the CPP chamber significantly increased preference for the non-preferred side of the chamber compared to that seen in home cage controls. Levels of circulating 3alpha-diol were increased significantly in 3alpha-diol>DHT>T-administered rats, compared to rats that had vehicle administered or androgen-administration discontinued. Androgen administration decreased seminal vesicle weight and intrahypothalamic androgen receptor (AR) binding compared to that seen in rats that had vehicle administered or androgen-administration discontinued. Testosterone, DHT, and 3alpha-diol decreased GABA-stimulated chloride influx in cortical synaptoneurosomes, and muscimol binding in the hippocampus compared to that seen in rats with vehicle administered or that had androgen-administration discontinued. These data indicate that administration of 3alpha-diol is more effective at enhancing CPP and increasing circulating 3alpha-diol levels than is DHT or T administration, and that all of the androgen regimens employed decreased peripheral and hypothalamic androgen receptor binding and cortical and hippocampal GABA(A) receptor function. Hence, whether the effects of 3 alpha-diol on CPP are mediated by differential actions at ARs or GABA(A) receptors in particular brain regions needs to be determined.

Differential effects of trihexyphenidyl on place preference conditioning and locomotor stimulant activity of cocaine and methamphetamine.

Cocaine produces rewarding and locomotor stimulant effects by increasing extracellular dopamine (DA) levels in the terminal areas of the mesolimbic DA system. Our recent in vitro studies have shown that a muscarinic receptor antagonist, trihexyphenidyl (THP) inhibits the binding of a cocaine analogue to the DA transporter at concentrations that are ineffective in inhibiting 3H-DA uptake, suggesting that THP may attenuate the actions of cocaine selectively. The present study examined whether THP could affect conditioned place preference (CPP) for and locomotor stimulant activity of cocaine and methamphetamine (MAP) in mice. Mice were injected with cocaine (10 mg/kg) or MAP (1 mg/kg) in one compartment of the CPP chamber 4 times every second day. On alternate days the animals received saline in the other compartment of the CPP chamber. Pretreatment with THP was made 10 min before cocaine or MAP injection. The CPP score and locomotor activity were assessed using a novel activity monitor, SCANET. Cocaine and MAP produced CPP for the drug-paired compartment. Pretreatment with THP (0.05-5 mg/kg) had no influence on cocaine-induced CPP at any dose tested. In contrast, MAP-induced CPP was completely antagonized by THP at 5 mg/kg, which produced no CPP by itself. Another muscarinic receptor antagonist, scopolamine (SCP, 3 mg/kg) neither caused CPP by itself nor affected the development of cocaine- or MAP-induced CPP. Both THP and SCP enhanced spontaneous, cocaine- or MAP-induced locomotor activity. Though the present conditioning treatments failed to develop locomotor sensitization to cocaine, THP, but not SCP, acted cooperatively with cocaine to develop locomotor sensitization. The development of locomotor sensitization to MAP was retarded by SCP but was not affected by THP. These results suggest that, contrary to our anticipation, THP has a unique characteristic of specifically counter-acting the rewarding properties of MAP via a non-cholinergic (muscarinic) mechanism.

A Study Examining Intravenous Ethanol‐Conditioned Place Preference in C57BL/6J Mice

The reinforcing effects of intravenous (I.V.) ethanol were examined in C57BL/6J (C57) mice with a conditioned-place-preference (CPP) paradigm. Before CPP testing, adult mice underwent jugular catheterization. On the following day, subjects were acclimated to a two-compartment CPP chamber. A 15-min nondrug pretest was conducted to determine compartment preference. For the treatment group, I.V. ethanol [30% (v/v), 3.4 microl/min, 25 min] was paired with the nonpreferred compartment, whereas I.V. saline was paired with the preferred compartment. The control group received I.V. saline in both compartments. Two conditioning sessions were conducted per day (0900 and 1500), and the order of the infusions was counterbalanced across subjects. The drug-free posttest was identical to the pretest, except that it occurred on the day after the final drug/compartment pairing. The entire procedure required 6 days. After just two pairings with ethanol, with a cumulative ethanol dose of only 0.82 g/kg/day, significant CPP was noted in the treatment group, whereas no change in compartment preference was noted for the control group. A separate group of C57 mice were trained to discriminate intraperitoneal ethanol (1.5 g/kg) from saline using a two-lever drug discrimination paradigm. After training was complete, these mice also underwent jugular catheterization. Substitution testing was conducted with I.V. ethanol [30% (v/v), 6.4 microl/min, 12 min] and saline. The results indicate that the subjective effects of ethanol did not differ according to the route of administration. Together, these experiments provide evidence that ethanol is rewarding for C57 mice, as indexed by ethanol CPP, and that the subjective effects of intravenously and intraperitoneally administered ethanol are similar.

A Study Examining Intravenous Ethanol-Conditioned Place Preference in C57BL/6J Mice

The reinforcing effects of intravenous (IV) ethanol were examined in C57BL/6J (C57) mice with a conditioned-place-preference (CPP) paradigm. Before CPP testing, adult mice underwent jugular catheterization. On the following day, subjects were acclimated to a two-compartment CPP chamber. A 15-min nondrug pretest was conducted to determine compartment preference. For the treatment group, IV ethanol [30% (v/v), 3.4 μl/min, 25 min] was paired with the nonpreferred compartment, whereas IV saline was paired with the preferred compartment. The control group received IV saline in both compartments. Two conditioning sessions were conducted per day (0900 and 1500), and the order of the infusions was counterbalanced across subjects. The drug-free posttest was identical to the pretest, except that it occurred on the day after the final drug/compartment pairing. The entire procedure required 6 days. After just two pairings with ethanol, with a cumulative ethanol dose of only 0.82 g/kg/day, significant CPP was noted in the treatment group, whereas no change in compartment preference was noted for the control group. A separate group of C57 mice were trained to discriminate intraperitoneal ethanol (1.5 g/kg) from saline using a two-lever drug discrimination paradigm. After training was complete, these mice also underwent jugular catheterization. Substitution testing was conducted with IV ethanol [30% (v/v), 6.4 μl/min, 12 min] and saline. The results indicate that the subjective effects of ethanol did not differ according to the route of administration. Together, these experiments provide evidence that ethanol is rewarding for C57 mice, as indexed by ethanol CPP, and that the subjective effects of intravenously and intraperitoneally administered ethanol are similar.