Baclofen, raclopride, and naltrexone differentially affect intake of fat/sucrose mixtures under limited access conditions

This study assessed the effects of the opioid antagonist naltrexone, the dopamine 2-like (D2) antagonist raclopride, and the GABA_B agonist baclofen on consumption of fat/sucrose mixtures (FSM) using a limited access protocol. Sixty male Sprague-Dawley rats were grouped according to two schedules of access (Daily [D] or Intermittent [I]) to an optional FSM. Each FSM was created by whipping 3.2% (L), 10% (M), or 32% (H) powdered sugar into 100% vegetable shortening in a w/w manner (n = 10 per group). One-hour intakes of the IL and IM groups were significantly greater than intakes of the respective DL and DM groups, thus fulfilling our operational definition of binge-type eating in these groups. Baclofen reduced intakes of the L and M mixtures regardless of access schedule, but failed to reduce intake of the H mixture. Naltrexone reduced intake in all groups, but potency was greater in IL rats than in DL rats. Furthermore, potency was attenuated in Intermittent rats, but enhanced in Daily rats, at higher sucrose concentrations. Raclopride reduced intake in the DL and stimulated intake in the IL groups, reduced intake in both M groups, and was without effect in both H groups. These results indicate that fat/sucrose mixtures containing relatively low concentrations of sucrose allow distinctions to be made between: 1) intakes stimulated by different access schedules and 2) opioid and dopaminergic modulation of those intakes. These results also suggest that brief bouts of food consumption involving fatty, sugar-rich foods may prove to be particularly resistant to pharmacological intervention.     

Increased sweet taste preference following the lesion of basolateral nucleus of amygdala (BLA) in rat

A study of gustatory preference was carried out in Wistar strain albino rats by electrolytically lesioning the basolateral nucleus of amygdala. The intake of sweet tasting saccharin (Sn-0.1% soln w/v), NaCl solutions (1% Soln w/v) and tap water, were tested in single bottle, 2 bottle choice and 3 bottle choice situations. The consumption of fluids both before and after the stereotaxic surgery was recorded and statistically analysed. Lesion of BLA increased the intake of all fluids in the single bottle tests (P < 0.01). But the increase in the group provided with saccharin was more than that in other two groups. When taste preference was tested using 2-bottle and 3-bottle choice situations, the lesioned rats were seeking Sn solution. In our previous study, we found that the lesion of BLA increased fluid intake in rats. The intake, in the present study was more in those animals provided with Sn solution. When choice was given, the rats shifted their preference from water to the Sn following the lesion. Thus this study confirms that BLA is involved in the preference for sweet tasting solution over the NaCl or plain water.     

Differential effects of saccharin supplementation on alcohol and water consumption by Wistar rats from different sources

The study was aimed to elucidate whether the dissimilar effects of concurrent presentation of sweet water on alcohol consumption previously reported for Wistar rats from different sources remain unchanged when alcohol is also flavored with 0.1% saccharin. Male Wistar rats from Laboratory of Experimental Biological Models (LEBM) and Krukovo animal farm (K) stocks having had 2 months free access to food, tap water, and 10% alcohol were given four consecutive two-bottle drinking tests: alcohol versus water, alcohol versus sweet water, sweet alcohol versus water, or sweet alcohol versus sweet water. The test order was quasi-random and each test lasted 4 days. In Wistar (K) rats, flavoring of either water or alcohol solution increased consumption of each of the fluids and decreased intake of concurrently available fluids. The elevation in water intake induced by its sweetening was antagonized by flavoring of alcohol solution. In Wistar (LEBM) rats, flavoring of either water or alcohol increased consumption of each of the fluid, but did not change the intake of alternative fluids. The stable alcohol consumption by Wistar (LEBM) rats and its suppression seen in Wistar (K) rats induced by concurrent presentation of flavored water parallel the patterns previously observed among P, sP, and HAD rats suggesting the existence among alcohol-consuming animals of typological diversity of alcohol motivation.     

Chronic sucrose intake enhances nicotine-induced antinociception in female but not male Long-Evans rats

Previous work has demonstrated that intake of palatable foods can alter the behavioral actions of opioid drugs. To investigate whether intake of palatable fare only affects opioid-induced behaviors or more generally influences drug-induced responses, this study examined the effects of chronic intake of a palatable sucrose solution on nicotine-induced antinociception. Eight male and eight female Long-Evans rats were provided with ground chow and water (control group), while eight males and eight females were provided with chow, water and a 32% sucrose solution (sucrose group). After 3 weeks of exposure to the dietary conditions, all rats were tested for nicotine-induced antinociception using the tail flick test. Nicotine, administered using a cumulative dose regime (0.03, 0.1, 0.3 and 1.0 mg/kg sc), led to dose-dependent increases in tail flick latencies in male and female rats. Females in the sucrose group displayed significantly greater antinociceptive responses to nicotine than those in the control group. Similar results were obtained when females were retested after an additional 2 weeks. Comparison of males and females, revealed that sucrose enhanced nicotine's antinociceptive action in female but not in male rats. While previous research suggested that sweet tasting substances might affect drug action by acting on the endogenous opioid system, the present results indicate that sucrose intake could also alter the cholinergic system and possibly other systems involved in nicotine antinociception.     

The effect of para-chlorophenylalanine on the intake of ethanol and saccharin solutions.

The effects of para-chlorophenylalanine (PCPA) on the ingestive behavior of rats offered a choice between ethanol (3%) and water, saccharin (0.125%) and water, or water alone were examined. Following a baseline period three saline or PCPA injections, 80 mg/kg, were administered. Decreases in both ethanol and saccharin intakes were observed. Increases in water intake occurred in the ethanol group without a change in total fluid intake. Increases in water intake did not occur in the saccharin group and these animals displayed decreases in total fluid intake. Water intake in the nonchoice group was unaffected. There were no changes in food intake associated with any of these effects. The data demonstrate that decreases in intakes following PCPA are not specific to ethanol solutions.     

Effects of the cannabinoid receptor antagonist SR 141716, alone and in combination with dexfenfluramine or naloxone, on food intake in rats

RATIONALE: Recent studies in animals have implicated endogenous cannabinoids in the regulation of palatable food intake, but it is not yet clear to what extent pharmacological agents acting on this system may have sustained actions and applicability to different feeding protocols. OBJECTIVES: In the present study, we examine the effects of the cannabinoid CB1 receptor antagonist SR 141716 on food intake of rats, and its behavioral specificity. We examine whether tolerance develops to the anorectic actions of SR 141716, and whether it has either additive or synergistic actions with dexfenfluramine or naloxone. METHODS: Undeprived rats were trained to eat a daily sweet milk dessert and on test days were administered single or combination drugs and intakes were recorded. In other studies, rats were deprived for 24 h of either food or water and intakes recorded after drug administration at the end of this time. In one study, rats were fed ad libitum chow with SR 141716 added. RESULTS: SR 141716 (1-3 mg/kg) suppressed both palatable food intake in undeprived rats and food, but not water, intake after deprivation. Using an isobolographic analysis, SR 141716 had an additive anorectic effect with dexfenfluramine. In contrast, SR 141716 in combination with naloxone had a significantly supra-additive anorectic action. SR 141716 was also effective orally and no tolerance to its anorectic effect developed over 3 days. CONCLUSIONS: These data show that SR 141716 is an effective anorectic agent using both palatable foods and bland chow, and is selective because water intake was unaffected. SR 141716 is also effective orally and has an effect sustained for at least several days. There appears to be a synergistic interaction between opioid and cannabinoid systems in the regulation of feeding, whereas the combination of a serotonin releasing agent and the CB1 antagonist is additive.     

Naltrexone does not prevent acquisition or expression of flavor preferences conditioned by fructose in rats

The effects of the general opioid antagonist, naltrexone, on the acquisition and expression of flavor preferences conditioned by the sweet taste of fructose were examined. Food-restricted rats were trained over eight daily alternating one-bottle sessions (2 h) to drink an 8% fructose solution containing one novel flavor (CS+/F) and a less preferred 0.2% saccharin solution containing a different flavor (CS-/S). Four groups of rats were treated daily with either saline (control group) or naltrexone doses of 0.1, 1.0, or 5.0 mg/kg during training. Preferences were assessed in two-bottle tests with the CS+/S and CS-/S flavors presented in 0.2% saccharin solutions following saline injections. Naltrexone dose-dependently reduced fructose and saccharin intakes during training, confirming the drug's well-known suppressive effect on the intake of sweet solutions. Despite their reduced training intakes, the naltrexone groups displayed preferences for the CS+/S over the CS-/S (72-86%) that were similar to that of the control group (78%). The effect of naltrexone on the expression of the CS+/S flavor preference was evaluated by treating control rats with naltrexone (0.1-5 mg/kg) prior to CS+/S vs. CS-/S choice tests. The drug doses produced a dose-dependent reduction in CS+/S intake but did not significantly attenuate the CS+/S preference. These data are consistent with the relative inability of naltrexone to reduce flavor-flavor conditioning by sucrose in sham-feeding rats and flavor-nutrient conditioning in rats receiving intragastric sucrose infusions. In contrast, dopamine antagonists reduce both sucrose- and fructose-conditioned flavor preferences, which indicates the sensitivity of these conditioning paradigms to neuropharmacological manipulations. These data indicate that the endogenous opioid system, unlike the dopamine system, does not play a major role in either the acquisition or expression of flavor preference learning as measured in two-bottle choice tests.     

Effects of ethanol and delta 9-tetrahydrocannabinol on phencyclidine disposition in dogs.

A three-way crossover study was performed to determine the influence of delta 9-tetrahydrocannabinol (THC) and ethanol (EtOH) separately upon phencyclidine (PCP) disposition in dogs. Seven dogs were given three single dose treatments: 1.5 mg PCP kg-1 i.v., 1.5 mg PCP kg-1 i.v. with 0.4 mg kg-1 THC i.v., and 1.5 mg PCP kg-1 i.v. with 1.25 g EtOH kg-1 i.v. PCP was measured in plasma samples collected for 24 h after administration of each treatment, with several pharmacokinetic parameters calculated from the plasma concentration vs time data. The PCP serum Cls values were significant change in V beta or t1/2. EtOH did not induce significant changes in any PCP pharmacokinetic parameter, although mean Cls and V beta were increased. These results confirm the observed THC inhibition of PCP metabolism, and suggest that the enhanced pharmacologic action of PCP by THC may result from higher serum PCP concentrations. These results further suggest that enhanced PCP actions by acute EtOH administration may result from increased PCP distribution to the CNS.     

Reduced alcohol drinking in adult rats exposed to sucrose during adolescence

Intake of sweet-alcoholic drinks during adolescence is believed to favor alcohol abuse and dependence in adulthood. This study examined the influence of early exposure to ethanol with or without sucrose on the consumption of sweet or alcoholic solutions in adulthood. Adolescent rats (from post-natal day 30-46) were given continuous free access to tap water and either 5% sucrose, 5% ethanol or mixed 5% sucrose-5% ethanol. The control group was given access to water only. Upon reaching adulthood (post-natal day 60), rats were tested for saccharin (sweet), quinine (bitter) and ethanol consumption using a two-bottle free-choice paradigm. The results indicated that pre-exposure to ethanol did not alter the intake of sweet or ethanol solutions in adulthood. However, rats exposed to sucrose during adolescence showed a decreased consumption of both sweet and ethanol solutions. Because alcohol has a sweet taste component, an additional group of rats, pre-exposed to either 5% sucrose or water during adolescence, was tested for intravenous ethanol self-administration (preventing oral sensory stimulation) and in a new model of simultaneous access to oral saccharin and intravenous ethanol that results in higher total ethanol intake. Relative to controls, sucrose-exposed rats showed reduced operant self-administration of saccharin, yet no differences were found for intravenous ethanol self-administration. Altogether, these findings indicate that sucrose exposure during adolescence persistently affected the perception of sweet taste reward and thereby alcohol’s acceptance in adulthood.     

Acquisition of oral phencyclidine (PCP) self-administration in rhesus monkeys: effects of dose and an alternative non-drug reinforcer

 The effects of drug dose and a non-drug alternative reinforcer on acquisition of oral PCP self-administration in rhesus monkeys were examined. Acquisition was studied using three groups of monkeys (seven subjects per group). One group received a low PCP dose (0.0375 mg/delivery) and the other two received a high PCP dose (0.15 mg/delivery). One of the high dose groups had concurrent access to a saccharin solution (0.03% w/v) and water during the intersession (17.5-h) period. Food non-restricted monkeys were initially given access to water under a fixed-ratio (FR) 1 schedule during daily 3-h sessions. Water was then replaced with PCP during the session. The monkeys were then reduced to 85% of their free-feeding body weights and fed before the session, and the FR value was increased from 1 to 2, 4 and 8. Subsequently, food was given post-session and water and PCP were available under concurrent FR 8 schedules. At this final step of the procedure, acquisition of PCP self-administration was considered to occur if PCP intake consistently exceeded water intake. When all three groups were given concurrent access to PCP and water, PCP intake was greater than water intake only in the group of monkeys receiving the high PCP dose. PCP intake increased when water replaced saccharin during intersession in the high PCP dose group. Within-group data revealed that 85.7% of monkeys acquired PCP reinforcement in the group given access to the high PCP dose while only 42.8% acquired in the other two groups. These data suggest that drug dose and presence of alternative non-drug reinforcers affect acquisition of drug self administration in non-human primates. Received: 14 May 1997 / Final version: 15 December 1997     

Effects of a selective mu opioid receptor agonist and naloxone on the intake of sodium chloride solutions

Endogenous opioid peptides are thought to play a role in mediating the palatability or rewarding aspects of sweet tastes. There is also evidence, however, which suggests that opioids may influence the preference for the taste of salt as well. In the present studies, we measured the effects of central administration of naloxone and the mu agonist [d-Ala²,MePhe⁴,Gly-ol⁵]enkephalin (DAGO) on the ingestion of salt solutions. In non-deprived rats given a choice of water and 0.6% saline, ICV injections of DAGO (1 and 3 nmol) significantly increased the intake of 0.6% saline; baseline water intake was minimal and was unaffected by DAGO. When rats were given a choice between water and 1.7% saline, DAGO stimulated both water and saline intake. Because 1.7% saline is a hypertonic solution, the increase in water intake may have been secondary to saline intake. In rats on a deprivation schedule in which water and 0.6% saline were available for only 2–3 h/day, there was a tendency for DAGO to increase 0.6% saline intake and decrease water intake, though these effects were not significant. In rats given water and 1.7% saline, DAGO increased saline intake and had no effect on water intake. Naloxone was also tested in water-deprived rats. Naloxone (20 and 50 µg) significantly decreased 0.6% saline intake; baseline water intake was low (3–5 ml) and was unaffected by naloxone. When rats were given a choice between water and 1.7% saline, naloxone (50 µg) significantly reduced water intake, while intake of 1.7% saline was slightly increased. These results suggest a role for central mu opioid receptors in mediating the preference for salt solutions.     

Effects of oral ethanol self-administration on the inhibition of the lever-press response in rats.

The effects of ethanol on the inhibition of a learned response were examined in adult, male Wistar rats from two treatment groups: oral self-administration of alcoholic solution (10% ethanol and 10% glucose in distilled water) and oral self-administration of sweet solution (10% glucose in distilled water). Subjects were food deprived and alcoholic or control solutions were available 1 h per day during 15 days. After this period, rats were tested in a two-bottle paradigm during 1 h per day and placed in the operant chambers immediately afterward. This phase went on for 19 days. Subjects were trained to lever press for food and were tested in a continuous reinforcement schedule, operant extinction, successive discrimination, and two-stimuli tests. Alcohol impaired the ability to inhibit previously reinforced responses but only in situations indicated by exteroceptive stimuli. Ethanol intake did not impair the lever-press behavior neither in the acquisition of the response nor in the continuous reinforcement schedule. These data suggest that the sedative effects of alcohol at this dose were not apparent in reinforcement situations, in contrast with extinction situations.     

Differences in the consumption of ethanol and flavored solutions in three strains of rats

Several studies have shown a correlation between ethanol consumption and the intake of flavored solutions in rats, particularly sweet solutions. This observation, however, has not been shown in all strains of rats. The present study examined whether the intake of ethanol and that of flavored solutions would be related in Lewis (LEW), Wistar (WIS), and Wistar Kyoto (WKY) rats. During phase I, all rats were presented with water and a flavored solution following a continuous access paradigm as developed by Overstreet et al.: quinine (0.25% wt/vol), saccharin (0.1% wt/vol), ethanol (ETOH) (10% vol/vol), and saccharin-quinine (SQ) solutions (0.4% wt/vol-0.04% wt/vol). During phase II, fluid presentations were reduced to a 10-min limited access schedule and were presented in the same order. Results showed strain differences in intake and preference for ETOH and SQ during both phases, but not in quinine or saccharin intake. ETOH and saccharin intake were only correlated in the LEW strain during limited access drinking, while ETOH and SQ intake were correlated in the LEW strain as well as when all strains were collapsed during continuous drinking. These findings suggested that any association between ETOH and sweet intake may not be generalizable to all rat strains. The animals used in this study may have differed in taste sensitivity, as low ETOH-consuming LEW rats were sensitive to the bitter taste of quinine alone, as well as when mixed with saccharin. Sensitivity to bitter tastes may be an important predictor of low ETOH consumption and/or preference. These data provide further evidence for the role of taste factors in the mediation of voluntary ETOH consumption in rats.     

Behavioral processes mediating phencyclidine-induced decreases in voluntary sucrose consumption

Prior exposure to phencyclidine (PCP) has been shown to decrease voluntary sucrose consumption in rats, which may indicate reduced reward function. To further characterize the effects of PCP on sucrose consumption, we examined the dose-response relationship between PCP and sucrose consumption, the longevity of the effect, the effects of repeated injections of PCP, variation of the PCP effect across sucrose concentrations, and the effects of PCP on gustatory hedonic responses. A single injection of PCP (2.5-20 mg/kg) dose-dependently suppressed sucrose consumption 20 h post-injection, with significant decreases after 15 and 20 mg/kg PCP. These decreases were sustained three days following withdrawal from PCP. Repeated injections of PCP (7.5 mg/kg bid for 7 days) decreased sucrose consumption 20 h after withdrawal, which returned to baseline on the second day. A single injection of PCP (15 mg/kg) suppressed 0.15 M sucrose more than 1 M sucrose consumption, with no effect on 0.3 M sucrose, suggesting that PCP suppressed intake of moderately rewarding taste stimuli. Finally, a single injection of PCP (15 mg/kg) suppressed brief access (20 s) licking for the majority of concentrations of sucrose solutions offered (0.031 M, 0.062 M, 0.125 M, 0.25 M, 0.5 M, and 1.0 M), while it had no effect on licking for 0.016 M sucrose, water, or for bitter quinine hydrochloride solutions (range: 0.94 mM-30 mM), suggesting that the PCP effect is specific to palatable taste stimuli without disruption of sensitivity to taste quality or intensity. We conclude that PCP produces moderate anhedonia as reflected through a specific decrease in the sustained consumption of moderately palatable sucrose solutions.     

Ethanol intakes and preferences in the desalivate rat

Desalivate and control rats were tested for ethanol versus water preference (5%, 10% and 20% (v/v) ethanol solutions). Each concentration of ethanol was presented for six days in an ascending, descending, or mixed presentation schedule. Following preference tests, intakes of first 10% (15 days), then 5% (15 days), and finally 10% (5 days) ethanol as the only available fluid were determined. Blood ethanol concentrations were measured (22:00 hr, 24:00 hr, 02:00 hr) during the final 10% ethanol intake test. Desalivate and control rats showed similar aversions to ethanol at all concentrations with relative ethanol intake being a negative function of concentration. During ethanol and water intake tests, desalivates drank significantly greater amounts (ml/100 g body weight) of all drinking fluids than controls. However, for both groups intake of 10% ethanol was reduced significantly from water baseline levels. Although desalivates consumed as much ethanol as controls, their blood ethanol concentrations at all times tested were slightly lower than controls. During the ethanol intake test desalivate rats lost body weight, while control rats gained body weight.     

Effects of body weight levels on cannabis self-injection

Previous findings have shown that naive rats self-inject IV delta 9-THC 12.5 microgram/kg/infusion in the presence of a FT-1 non contingent food delivery schedule. In the present study the effects of three different body weight levels, 80%, 90% and 100%, with and without a FT-1 food delivery schedule, were examined on the THC self-injection behavior. Results confirmed that 80% body weight plus the FT-1 schedule condition leads to the highest intake of THC. In a further experiment, naive rats acquired THC self-injection at 80% body weight with a FT-1 schedule. Rats were then allowed to regain body weight to their free feeding level and were tested again in the same basic paradigm. Animals recovering body weight did not maintain the self-injection rates. The data indicate that the environmental conditions necessary in the acquisition phase are also required to maintain intake of THC 12.5 microgram/kg/infusion.     

The benzodiazepine inverse agonist RO19-4603 exerts prolonged and selective suppression of ethanol intake in alcohol-preferring (P) rats

The time course of the benzodiazepine (BDZ) inverse agonist RO19-4603 in antagonizing ethanol (EtOH) intake was investigated in alcohol-preferring (P) rats (n=7) maintained on 24-h continuous free-choice access to EtOH (10% v/v), water, and food. After fluid intakes had stabilized over several weeks, animals were injected with Tween-80 vehicle solution or RO19-4603 (0.075, 0.150, and 0.30 mg/kg). EtOH and water intakes were determined at 8- and 24-h intervals. RO19-4603 caused a marked attenuation of EtOH drinking with each of the doses tested. EtOH intake during the 8-h following 0.075, 0.150, and 0.30 mg/kg RO19-4603 was decreased by approximately 36, 74, and 57%, respectively. Intakes during the 24-h interval were similar to the vehicle control condition. However, 32 h post-drug administration, EtOH intakes were reduced to approximately 27, 31, and 29% following the 0.075, 0.150 and 0.30 mg/kg doses, respectively. To further confirm the reliability of the RO19-4603 dose-response effect, and its selectivity for EtOH, the highest dose condition (0.30 mg/kg) was tested twice. The second 0.30 mg/kg dose condition exerted a profile of effects similar to the initial treatment; 8 h following administration, intake was decreased to 60% of the control level, and 32 h post-drug administration intake was decreased to approximately 46% of the controls. These decreases were evidently selective in comparison with water, since water drinking showed compensatory increases which paralleled the decreased EtOH consumption. Dose-response comparisons indicated that 0.150 mg/kg approaches the maximum effective dose, since the 0.30 mg/kg dose of RO19-4603 did not produce an additional decrease in EtOH intake. Furthermore, unlike the lower doses, the 0.30 mg/kg dose failed to yield reliable compensatory increases in water drinking. The results demonstrated that a single acute administration of RO19-4603 produces prolonged and selective suppression of EtOH intake in P rats maintained on 24-h continuous free access to EtOH. While it is not clear at present what properties of the ligand might explain the observed effects on EtOH intake, these findings along with our previous work, clearly suggest that RO19-4603 may modify neuronal processes that promote EtOH self-administration. Neural transmission at the GABA_A-BDZ receptor complex may play an important role in mediating EtOH reinforcement.     

Metabolic interactions of phencyclidine (PCP) and delta 9-tetrahydrocannabinol (THC) in the rat

The in vitro effects of THC on the metabolism of PCP by rat liver were determined. Samples containing 1 mM PCP were incubated for 1 hr at 37 degrees C with an NADPH-generating system containing 10,000 X g supernatant or Ca++-precipitated rat liver microsomes. These incubations were carried out in the presence or absence of THC and at the end of 1 hr, PCP metabolites were determined by gas chromatography. In the presence of 0.1, 0.05, 0.025 and 0.0125 mM THC, the production of 1-(1-phenyl-4-hydroxycyclohexyl)piperidine (metabolite I) by the 10,000 X g supernatant was decreased by 46, 29, 23 and 16% respectively. Similarly, production of 1-(1-phenylcyclohexyl)-4-hydroxypiperidine (metabolite II) was reduced significantly by 58, 44, 34 and 23% with the respective concentrations of THC. However, the production of 1-phenylcyclohexylamine (metabolite III) was increased by 18, 32, 30 and 22% with 0.1, 0.05, 0.025 and 0.0125 mM THC. Incubations with Ca++-precipitated liver microsomes revealed similar trends in PCP metabolism in the presence or absence of THC. Metabolites I and II were reduced by 62 and 67% by 0.1 mM THC. Another concentration of THC (0.025 mM) caused a 50 and 62% decrease in I and II. These observations suggest that THC alters the in vitro microsomal metabolism of PCP.     

Differential effects of CGS 8216 and naltrexone on ingestional behaviour

Effects of the pyrazoloquinoline CGS 8216 (a partial benzodiazepine receptor inverse agonist) and the opiate antagonist, naltrexone, were compared in several tests of ingestion in non-deprived and deprived male rats. Both naltrexone (0.1-10.0 mg/kg, SC) and CGS 8216 (1.25-10.0 mg/kg, IP) significantly reduced the consumption of a highly palatable saccharin-glucose solution by non-deprived rats. Both compounds were also effective in reducing, dose-dependently, the intake of palatable sweet or oily mash by non-deprived animals. Hence, naltrexone and CGS 8216 attenuated palatability-induced ingestional responses, and sweet taste was not necessary for this effect to occur. The two drugs also reduced the intake of the saccharin-glucose solution in food-deprived rats, but their effects diverged in water-deprived animals. CGS 8216 had relatively little effect in the thirsty animals, whereas the effect of naltrexone was enhanced. This difference was underscored in a final test of deprivation-induced consumption of water. Naltrexone reduced the drinking, but CGS 8216 had no effect. Taken together, these data indicate that CGS 8216 was more selective in its effects on ingestion.     

Methylenedioxymethamphetamine's capacity to establish place preferences and modify intake of an alcoholic beverage

Doses of 0.2, 2.0, 6.3 and 20.0 mg/kg 3,4-methylenedioxymethamphetamine (MDMA), a putative neurotoxin at serotonergic neurons and a recreational drug, were assessed using Sprague-Dawley rats in the conditioned place preference (CPP) test. Also, the drug's effects on intake of a sweetened ethanol solution (ES) was assessed. The CP testing involved multiple administrations of MDMA with frequent periodic testing (weekly for 4 weeks) of MDMA's effects. Doses of 2.0 and 6.3 mg/kg produced positive CPPs with every test. MDMA also affected rats' gain in body weight across the 4 weeks of dosing. The 2.0 mg/kg reliably incremented gain in body weight, while the 20.0 mg/kg dose reliably attenuated it. In the drinking experiment, water-deprived rats (22 h/day) were given daily opportunities to drink either tap water or a sweetened ES. When stable intakes were achieved, MDMA's effects were assessed across repeated daily administrations (12 days) and subsequently (16 days). MDMA, dose-relatedly, decreased intake of both ES and water with the highest dose leading to marked loss in body weight. Intakes of fluids were not modified markedly subsequent to dosing. In summary, MDMA is an agent that produces a positive CPP (providing further evidence for MDMA's abuse liability), produces changes in weight gain and nonselectively reduces fluid intake among fluid-deprived rats.