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Post by danlirette on Nov 1, 2007 0:20:47 GMT -5
Rodents get drunk as skunks off seized liquor Authorities in India say rats are gnawing at beer cans and making holes in caps of whisky bottles stored in police storehouses in the east of the country and apparently getting drunk. Kundan Krishnan, a senior officer says the rodents' love for liquor has the police department in Bihar state stumped as it tries to store hundreds of bottles seized from illegal sellers from across the state in Patna, the state capital. "We are fed up with these drunk rats and cannot explain why they have suddenly turned to consumption of alcohol," he said. The problem costs revenue as the seized liquor is usually sold through auctions, he said. Rats were also attacking people near the police buildings, nibbling at their toes, although it was not clear if they were under the influence, officials and witnesses said. www.abc.net.au/news/stories/2007/06/21/1958600.htm
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Post by celebrity on Nov 7, 2007 17:14:02 GMT -5
I took pharmacology of psychology last semester.
And we covered rat experiments in a few of our studies. Rats addict easily to many things but oddly enough will stop being addicted to others. The question our professor asked us.
Are rats smarter than humans? She seemed to think so this is a general idea from 2 professors. If I can I will find some more rat studies involving differing drugs.
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Post by celebrity on Nov 7, 2007 17:29:56 GMT -5
Okay I am sending you thing from psychinfo. I am not sure if it will print but I wanted to show you how complicated this stuff gets. If you can read this, you missed your call and should be a psychologist. I cut half of the artical cause of lengh.
Methylenedioxymethamphetamine and cocaine on conditioned place preference in the adult male rat
Anna J. Dillera, Angelica Rochaa, Aaron L. Cardona, Rodrigo Vallesa, Paul J. Wellmana and Jack R. Nation, a, aDepartment of Psychology, Texas A&M University, College Station, TX 77843, United States Received 4 June 2007; revised 11 July 2007; accepted 27 July 2007. Available online 8 August 2007.
Abstract Conditioned place preference (CPP), a commonly used model for studying the role of contextual cues in drug reward and drug seeking, was employed to explore possible behavioral interactions between (±)3,4-methylenedioxymethamphetamine (MDMA; “ecstasy”) and cocaine. On each of four occasions, adult male rats received one of three doses of MDMA (0 mg/kg, 5 mg/kg, 10 mg/kg; administered subcutaneously [s.c.]) combined with one of three doses of cocaine (0 mg/kg, 2.5 mg/kg, 5 mg/kg; administered intraperitoneally [i.p.]), and were then tested in a CPP paradigm. The results showed MDMA-induced CPP at a unit dose of 5 mg/kg, but at the 10 mg/kg dose there was a return to baseline (control) performance levels. For cocaine alone, CPP increased in a linear fashion as the drug dose was increased. Concurrent administration resulted in antagonism of each drug, but there was evidence that this pattern was reversible at higher doses of the respective drugs. These data are instructive insofar as they suggest that the behavioral and neurochemical effects of MDMA and cocaine presented in isolation are dramatically altered when the two drugs are presented in combination.
1. Introduction Although (±)3,4-methylenedioxymethamphetamine (MDMA; “ecstasy”) is an illegal substance, it is gaining global popularity as a recreational drug, especially in youth culture and at all-night dance parties known as “raves” ([Clemens et al., 2004], [Forsyth, 1996], [Green et al., 1995], [Peroutka, 1987], [Schechter, 1991] and [Schenk et al., 2003]). Although the epidemiology of polydrug use involving MDMA has not been adequately characterized, reports are available which suggest that on occasion MDMA is used in combination with cocaine (e.g., Parrott et al., 2000). Because preclinical studies have focused on the longterm consequences of MDMA pretreatment on subsequent cocaine administration (e.g., [Achat-Mendes et al., 2003] and [Horan et al., 2000]), more explicit information on the interactive profile of concomitant exposure to MDMA and cocaine is required.
There are several lines of research that underscore the need to examine possible MDMA/cocaine interactions. Dopamine (DA) has been implicated as mediating the stimulatory effects of cocaine, which acts as a DA transporter inhibitor (blocking presynaptic reuptake and thus increasing DA availability at D1-like and D2-like postsynaptic receptors [Riley, 1995]), therein producing reward by enhancing dopaminergic transmission in the nucleus accumbens [NAcc] ([Heidbreder et al., 1996], [Kalivas and Duffy, 1993] and [Pettit et al., 1990]). In contrast to cocaine, MDMA activates DA release by stimulating serotonin (5-hydroxytryptamine [5HT]) receptors (Müller et al., 2007), and reverses rather than blocks the DA transporter (DAT) and serotonin transporter (SERT); cf. Rothman and Baumann, 2003. The preferential action of MDMA at the SERT site is of particular significance because manipulations that increase 5-HT function decrease cocaine and amphetamine self-administration ([Carroll et al., 1990], [Howell and Byrd, 1995], [Smith et al., 1986] and [Wee et al., 2005]). In addition, single gene knockout of SERT has been shown to increase the rewarding properties of cocaine, ostensibly because stimulated actions at SERT are at least partially aversive (Uhl et al., 2002), or modulate DA activity (Hall et al., 2004). Paradoxically, and contrary to what has been argued elsewhere (Colado et al., 2004), these data suggest the combined use of MDMA and cocaine in the human population may result in antagonism of the rewarding properties of one or both drugs.
One method for indexing the relative rewarding properties of different psychoactive drugs involves conditioned place preference (CPP). There is general agreement that the CPP model affords a valid assessment of parameters common to drug reward and drug seeking (e.g., [Bardo and Bevins, 2003], [Cervo et al., 2002] and [Knapp et al., 2002]). The CPP paradigm is based on classical (Pavlovian) conditioning principles, as contextual cues acquire secondary reinforcing (conditioned stimulus [CS]) properties through temporal pairing with a psychoactive drug that functions as an unconditioned stimulus [US] (Calcagnetti and Schechter, 1993). In this model, a drug is administered to an animal immediately before placement in an environment with distinctive contextual stimuli (olfactory, visual, tactile). Place preference is then defined by some measure of preference for one environment over another based on feed-forward conditioning (see Bardo and Bevins, 2003).
MDMA and cocaine, presented separately at low doses, have been shown to elicit CPP in rats ([Bardo et al., 1995], [Cole et al., 2003] and [Schechter, 1991]). Interestingly, a purportedly neurotoxic dose of MDMA (20 mg/kg, s.c.) administered prior to MDMA CPP testing significantly decreased conditioning at lower doses of the test dose, but not at higher doses of the test dose (Schechter, 1991). More directly related to the rationale that formed the basis for the present investigation, a recent report by Aberg et al. (2007) showed that for adult rats cocaine-induced (10 mg/kg) CPP was diminished by MDMA administered five days prior to CPP training. However, in this study only a single dose of cocaine was tested and there was no attempt to determine the effects of cojoint exposure, which as noted above is the more likely pattern of exposure among young adults. Moreover, the effects of cocaine on MDMA CPP have never been examined. Accordingly, the purpose of this investigation was to systematically characterize the dose-effect pattern produced by the combined administration of both MDMA and cocaine in a CPP preparation, and explicitly determine if synergism occurs when the two drugs are presented concurrently, as some clinical consumption patterns suggest ([Block et al., 2002], [Gross et al., 2002] and [Smit et al., 2002]), or if antagonism occurs as suggested by the preclinical literature on DA and 5-HT function (cf. Rothman and Baumann, 2003).
2. Methods 2.1. Animals Adult male Sprague-Dawley rats (n = 63), weighing ≈ 250–300 g at the start of the experiment, were obtained from a commercial source (Harlan; Houston, TX). All animals were provided standard laboratory rat chow (Teklad; Madison, WI) and tap water ad libitum throughout the course of the experiment, and were housed individually in plastic cages. Animals were not presented with food or water in the test chambers. A 12 h/12 h light–dark cycle was used (lights on at 08:00 h), with temperature held constant at 23 °C in the holding area and test room. Beginning one week prior to the start of the experiment, animals were handled daily to limit any confounding variables caused by handling stress during the conditioning or experimental procedures. Body weights were recorded daily throughout the experiment.
The animal housing and testing facility was approved by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International), and all animal maintenance, research design, and administration was conducted in accordance with guidelines provided by the Texas A&M University Laboratory Animal Care Committee (ULACC). All aspects of the research were conducted in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (Publication No. 85-23, revised 1985). The health of the animals was monitored by the campus veterinarian throughout the duration of the project.
2.3. Drugs The Research Technology Branch of the National Institute on Drug Abuse (NIDA) provided cocaine HCl and MDMA HCl gratis. Cocaine HCl and racemic MDMA [(±)-MDMA HCl] were dissolved in a 0.9% w/v saline vehicle, and the doses were expressed as the salt. Cocaine was administered i.p. and MDMA was administered s.c.; all drugs were delivered in a volume of 1 ml/kg.
2.4. Procedure The CPP experiment started immediately following one week of acclimation to the laboratory environment. The biased CPP procedure employed in this study consisted of a sequence of three phases as outlined by Schechter (1991). The first phase was the preconditioning phase that served to establish a baseline place preference for each rat. On Day 1, animals were transferred in tubs from the colony room to the testing chambers for 20 min in an effort to habituate the animals to transportation and the sound and illumination of the room. Animals were placed in the apparatus and allowed free access between compartments during the 20-min period to overcome freezing effects from exposure to a novel environment. Data recorded from the first day were not used in calculating the preferred side. Between tests, each conditioning apparatus was cleaned thoroughly to eliminate confounding scent cues. On Day 2, animals were placed in the CPP apparatus and allowed free access to either compartment for 15 min in order to establish their baseline preference. Pretest data were measured by the amount of time (min) animals spent in each compartment, and these data were used to determine animal pretest preferences for the white or black compartment.
The conditioning phase consisted of 8 days of repeatedly pairing one specific compartment with an injection of either drug or vehicle. By individually analyzing data from baseline day (Day 2) testing, the most-preferred and least-preferred sides were determined for each rat. On four alternate days (Days 3, 5, 7, and 9), each animal received a daily s.c. injection of its respective combination of MDMA (0, 5, or 10 mg/kg body weight) 25 min before an i.p. cocaine injection (0, 2.5, or 5 mg/kg body weight). The resulting interaction of 3 doses of MDMA × 3 doses of cocaine created 9 groups; 0 M (0 mg/kg MDMA)–0 C (0 mg/kg cocaine) (n = 7), 0 M–2.5 C (n = 7), 0 M–5 C (n = 7), 5 M–0 C (n = 7), 5 M–2.5 C (n = 7), 5 M–5 C (n = 7), 10 M–0 C (n = 7), 10 M–2.5 C (n = 7), and 10 M–5 C (n = 7). The time delay between the MDMA injections and the cocaine injections that were administered immediately prior to testing was based on the slow onset of the physiological effects of MDMA, relative to cocaine (Schechter, 1991).
Animals were confined to the least-preferred compartment (defined as the compartment in which the animal spent the least amount of time on the Day 2 pretest) for 20 min immediately after the injections of MDMA/cocaine combinations. On the other four alternate days (days 4, 6, 8, and 10), all animals received s.c. and i.p. vehicle (saline) injections and were confined to the most-preferred compartment (defined as the compartment in which the animal spent the most amount of time on the Day 2 pretest) for 20 min at the same post-administration time. As noted, all injections were given at a volume of 1 ml/kg vehicle. Animals were run in squads of seven, counterbalanced by drug group assignments and weight.
In the final phase (Day 11), to determine post-conditioned preference, posttest data were obtained using the same procedure as the Day 2 pretest, i.e., in the absence of an injection, subjects were permitted 15 min of free access between the distinctive chambers of the test apparatus. Weight-sensitive flooring in the place preference apparatus recorded the amount of time spent in each chamber.
2.5. Statistical analysis The pretest data from Day 2 and the posttest data from Day 11 were examined. The conditioning scores in both experiments were defined by the number of min spent on the drug-conditioned compartment on posttest trial minus the number of min spent on the same compartment in the pretest trial. Subject weight was analyzed using a repeated measures analysis of variance (ANOVA) test with daily body weight averages during the testing period serving as the within factor. The behavioral data were analyzed by a 3 doses of MDMA (0 mg/kg, 5 mg/kg, 10 mg/kg) × 3 doses of cocaine (0 mg/kg, 2.5 mg/kg, 5 mg/kg) completely factorial ANOVA. Neuman–Keuls procedure for post hoc analyses was employed for individual comparisons.
During conditioning and prior to testing, one male rat in the 10 M–0 C condition exhibited decreased muscle tone, nonresponsiveness, rapid heart rate, shallow breathing, frothing at the mouth, and temporary paralysis. This animal fully recovered and because the data from this rat were not appreciably different from other animals in the 10 M–0 C condition, these data were included in the analyses reported here.
3. Results 3.1. Body weights Consistent with earlier reports (e.g., [Bilsky et al., 1990] and [Bilsky et al., 1991]), there was a systematic trend toward weight loss among animals exposed to 10 mg/kg MDMA. However, the difference in group means was not large (305.6 g for groups receiving 10 mg/kg MDMA compared to 317.6 g for groups receiving 0 mg/kg MDMA). This trend toward weight loss was not evident among animals exposed to cocaine.
3.2. Behavioral data Despite attempts to limit preferences for the black compartment of the apparatus, the majority of animals in all conditions demonstrated an initial preference for this side of the test chamber during pretesting (Day 2). The conditions did not differ with respect to preference ratios. In terms of the test results, findings from a 3 doses of MDMA (0 mg/kg, 5 mg/kg, 10 mg/kg) × 3 doses of cocaine ANOVA showed the main effects for MDMA dose (F(2,54) = 5.43, p < 0.01) and cocaine dose (F(2,54) = 3.29, p < 0.05) reached an acceptable level for statistical significance. Further examination of the data confirmed that these main effect differences were byproducts of a significant interaction between MDMA and cocaine doses (F(4,54) =7.51, p < 0.01). Subsequent comparisons of individual group means showed cocaine administered singularly (at a 0 MDMA dose) produced a standard dose-effect curve; significant differences from saline were evident at both 2.5 mg/kg and 5 mg/kg; p < 0.05 (see Fig. 1). At a 5 mg/kg dose of MDMA, increasing doses of cocaine resulted in increasing antagonism (declines) of CPP. Interestingly, at the highest dose of MDMA (10 mg/kg) the pattern of antagonism was reversed, i.e., CPP increased as cocaine dose increased. These data suggest a complex pattern wherein cocaine has antagonistic effects at lower doses of MDMA, but this pattern is reversed at higher doses of MDMA.
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Post by celebrity on Nov 8, 2007 15:28:35 GMT -5
As you see from scientific writting, that it is hard to determine what is said between the abreviations and numbers. Most people looking for what a study means goes right to the results section or the abstract every thing in the introduction is proof from another persons point of view.
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