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| #184 Poster Session - BPH |
| Sunday, May 29, 2005 |
| 12:00 PM–1:30 PM |
| Southwest Exhibit Hall (Lower Level) |
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| 33. A Novel Model of Drug-Induced Reinstatement |
| Area: BPH; Domain: Applied Research |
| RICHARD W. FOLTIN (New York State Psychiatric Institute), Stephanie Collins (New York State Psychiatric Institute), Margaret Haney (New York State Psychiatric Institute), Suzette M. Evans (New York State Psychiatric Institute) |
| Abstract: The purpose of this study was to develop a laboratory model of reinstatement that more closely approximates relapse in human drug users. Four adult female rhesus monkeys, implanted with intravenous (IV) access ports, were trained to self-administer IV cocaine (0.0125 - 0.1 mg/kg/infusion) during 2-hr sessions 4 days a week, during which responding was maintained under a progressive ratio (PR) schedule of reinforcement with a maximum of 10 drug deliveries. The starting ratio and ratio increment varied among monkeys so that 7-9 infusions were received under the 0.1 mg/kg condition. The breakpoint increased as a function of cocaine dose. Extinction was accomplished two ways: extinction of cues and cocaine by substituting saline, and extinction of cocaine only by removing cocaine and the cue lights paired with cocaine, a situation that is not observed in humans. Cues were effective in increasing responding maintained by saline only when they had not been extinguished. Response-independent cocaine increased responding maintained by saline under both extinction conditions. Reinstatement studies using laboratory animals deliver response-independent drug prior to a session when saline is available, while humans rarely take placebo. When cocaine was available during a single session after extinction, response-independent cocaine increased responding maintained by low, but not by high doses of cocaine. These findings suggest that studies that fail to extinguish drug-paired cues may over-estimate the role of cues in inducing relapse, and that response-independent cocaine increases the reinforcing efficacy of low cocaine doses.Funded by U.S. NIH Grant DA-12675 |
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| 34. Dose Intermittency and the Stability of a Cocaine Dose-Response Curve |
| Area: BPH; Domain: Basic Research |
| JULIE A. MARUSICH (University of Florida), Marc N. Branch (University of Florida) |
| Abstract: The purpose of the present experiment was to assess the stability of dose-response effects of cocaine when drug administrations occurred at weekly intervals, and then at four day intervals. Pigeons pecked on a fixed ratio 20 (FR 20) schedule. Subjects were randomly assigned to a Descending dose-order or Ascending dose-order Group. All subjects were administered a dose of cocaine or saline vehicle every seventh day in phase 1. The dose-response function was assessed 8 consecutive times to assess the stability of effects of each dose. Four of 6 subjects’ dose-response curves were stable across the 8 cycles of doses used in dose-response curve construction, indicating that administration of acute doses spaced 7 days apart is unlikely to produce tolerance to effects of cocaine. The second phase of the experiment examined effects of doses spaced 4 days apart with the same subjects. |
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| 35. The Discriminative Stimulus Effects of 22 Hours Food Restriction in Rats |
| Area: BPH; Domain: Basic Research |
| DAVID C. JEWETT (University of Wisconsin-Eau Claire), Valerie Jonjak (University of Wisconsin-Eau Claire), Sarah Weis (University of Wisconsin-Eau Claire), Natalie R. Koffarnus (University of Wisconsin-Eau Claire), Regina Carroll (University of Wisconsin-Eau Claire), Daniel Hehli (University of Wisconsin-Eau Claire), Martha Grace (University of Minnesota), Allen Levine (University of Minnesota) |
| Abstract: We trained rats to discriminate between 2 and 22 hrs of acute food restriction in an operant choice paradigm. During generalization tests, acute food restriction produced time-dependent increases in 22 hr responding. During other tests, rats were food restricted for 22 hrs and responded appropriately. When rats were then given access to food for 20 minutes and again placed in the operant test, rats reliably selected the lever associated with 2 hrs food restriction, indicating that food consumption eliminates discriminative stimuli associated with 22 hrs food restriction. Under similar test conditions, consumption of either saccharin or sucrose did not alter the discriminative stimulus effects of 22 hrs food restriction. During other tests, rats were food restricted for 2 hrs and responded appropriately. Rats were given hypothalamic injections of neuropeptide Y (NPY), ghrelin, or saline. NPY and ghrelin produced dose-dependent increases in 22 hr-appropriate responding. These findings suggest that discriminative stimuli produced by 22 hrs food restriction are mimicked by neurochemicals administered into brain areas important for feeding regulation. These effects may serve as a model to examine factors that alter internal stimuli associated with eating |
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| 36. The Effects of Muscarinic Acetylcholine Receptor Antagonism in the Ventral Tegmental Area on Food Reward in Rats |
| Area: BPH; Domain: Basic Research |
| RUTH SHARF (Queens College, City University of New York), Robert Ranaldi (Queens College, City University of New York) |
| Abstract: Stimulation of muscarinic acetylcholine receptors (mAChR) in the ventral tegmental area (VTA) excites dopamine neurons and appears to be necessary for eating. We investigated the role of VTA mAChR in operant responding maintained by food reward and eating. In experiment 1, six rats, prepared with bilateral guide cannulae to allow for microinjections in the VTA, were trained to press a lever under a progressive ratio schedule of reinforcement and tested with intracerebral injections of scopolamine, an M1/M2 mAChR antagonist. Microinjections of scopolamine (0, 2.5, 5, 20, and 40 µg/0.5 µl) into the VTA did not cause significant effects on lever pressing. In experiment 2, eighteen rats were pretreated with intra-VTA scopolamine (0 or 5 µg/0.5 µl) prior to being placed in conditioning chambers on each of four consecutive 60-min sessions, each held on consecutive days. During each of these sessions, animals were exposed to 81 presentations of a 3-s light stimulus, where a randomly determined one third of these were followed by delivery of two 45-mg food pellets. Animals pretreated with 0 µg/0.5 µl scopolamine ate all the food pellets. Animals pretreated with 5 µg/0.5 µl scopolamine ate significantly fewer pellets than vehicle controls (P<.001), suggesting a role of mAChR in eating. Altogether, these data suggest that scopolamine disrupts eating but not food-rewarded lever pressing. |
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| 37. Changes in Response Topography and Sensitivity to Reward During Exposure to DA D1, D2 and D3 Receptor Agonists |
| Area: BPH; Domain: Basic Research |
| VALERI FARMER-DOUGAN (Illinois State University), Katie Freske (Illinois State University), Sarah Davis (Illinois State University), Melanie Grzesik (Illinois State University), Corinne Smith (Illinois State University), Seshanand Chandrashekar (Illinois State University) |
| Abstract: Dopamine D1, D2 and D3 receptors may have differential effects on reward behavior. DA D1 receptors may be part of a feedback loop about reward. In contrast, DA D2 receptors may regulate overall response rates, not reward sensitivity. The role of DA D3 receptors is less clear. Research from our lab offers support for these hypotheses: Changes in sensitivity to reward during DA D1 and D2 agonist exposure were correlated with changes in behavioral topography differentially produced by the two agonists. D1 agonist-induced changes in sniffing, grooming, or general search behaviors detracted from operant responding and reduced sensitivity to reward. In contrast, D2 agonist exposure had less effect on sensitivity to reward, but resulted in an overall response reduction. The present study extends this research. Changes in response topography were examined during exposure to a DA D1 agonist (SKF 38393), a D2 agonist (quinpirole), and a D3 agonist (PD128095) across a series of concurrent VI VI schedules. Rates of individual behaviors during baseline, saline, and at each drug dose were obtained. The three drugs elicited topographically different response repertoires correlating with differences in sensitivity to reward. These data further establish how specific DA receptor activity modulates choice behavior. |
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| 38. Effects of Clomipramine on Self-Control Choice in Lewis and Fischer 344 Rats |
| Area: BPH; Domain: Basic Research |
| KAREN G. ANDERSON (West Virginia University) |
| Abstract: Rates of delay discounting (impulsive choice) have been shown to vary among individuals, particularly people who abuse drugs relative to those who do not, but factors that may contribute to these differences have not been identified. To explore a role for possible genetic and neurochemical determinants, Lewis (n=8) and Fischer 344 (n=8) rats were allowed to choose between one food pellet delivered immediately and three food pellets delivered after increasing delays. The delays to the large reinforcer (0, 10, 20, 40, 60 s) were increased across five blocks of trials in daily experimental sessions. For both groups of rats, choice for the larger reinforcer decreased as the delay to presentation increased. However, the Lewis rats were more likely to choose the smaller, immediate reinforcer earlier in the session, i.e., at shorter large-reinforcer delays, than the Fisher 344 rats. This difference in choice was statistically significant. Repeated administration of 3.0 mg/kg, i.p. clomipramine (mean of last five sessions) did not significantly alter choice, relative to baseline, for either strain. The present findings suggest that differences in delay discounting/impulsive choice may involve genetic, e.g., neurochemical, differences. |
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| 39. The Effects of Clinically-Relevant Doses of Amphetamine and Methylphenidate on Self-Control, Impulsivity, and Attention |
| Area: BPH; Domain: Basic Research |
| ROBERT C. SPENCER (University of Wisconsin-Madison), Matthew E. Andrzejewski (University of Wisconsin-Madison), Ann E. Kelley (University of Wisconsin-Madison), Craig Berridge (University of Wisconsin-Madison) |
| Abstract: Attention Deficit Hyperactivity Disorder (ADHD) is characterized by impulsivity, inattentiveness and hyperactivity. The effects of clinically relevant doses of the stimulants amphetamine (.1 mg/kg) and methylphenidate (.5 mg/kg) were evaluated using four operant tasks previously reported as measures of at least one of these symptoms. The effects of these stimulants on impulsivity and self control were assessed using the behavioral contingencies of differential reinforcement of low levels of responding (DRL) and differential reinforcement of other behavior (DRO). Interperitoneal administration of neither amphetamine nor Ritalin proved effective in improving performance on these tasks. A third task previously reported as a measure of self control in which rats were given repeated choices between a single, immediately available reinforcer, or three reinforcers after a delay was similarly unaffected by the prior administration of either stimulant. Finally, a signal detection task was employed to test the effects of stimulants on vigilance. While amphetamine has been shown to improve performance on this task before, we found that both Ritalin and amphetamine improved performance as measured by d’. |
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| 40. Choice Between Immediate and Delayed Reinforcement in Alcohol Self-Administration |
| Area: BPH; Domain: Basic Research |
| FORREST J. FILES (Bradley University) |
| Abstract: To study the reinforcing functions of alcohol, animals are trained to self-administer alcohol using the sucrose-substitution technique. Once established, self-administration can be used to determine whether the drug reinforcer functions as do other known reinforcers. This study explores whether rats will choose a small, immediately presented quantity of alcohol or a larger quantity of alcohol presented after various delays. Eight Long-Evans rats were trained to self-administer a 10% (v/v) alcohol solution. After training on one lever, a second lever was introduced. Responding on one lever resulted in the presentation of one dipper of alcohol while responding on the other lever resulted in the presentation of three dippers. Results indicated that when given a choice between an immediate large reinforcer and an immediate small reinforcer, rats consistently chose the large reinforcer. Preliminary data suggest that when a delay is imposed before the large reinforcer, preference shifts to the small, immediate reinforcer as the delay is lengthened. The results will be discussed in terms of the similarity of alcohol and food reinforcement in this paradigm. |
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| 41. Time Allocation on a Four Random-Interval Concurrent Schedule: Effects of Free Water and Alcohol Availability |
| Area: BPH; Domain: Basic Research |
| ELIAS ROBLES (University of Arkansas for Medical Sciences), Wilson Howe (University of Arkansas for Medical Sciences), William Wessinger (University of Arkansas for Medical Sciences) |
| Abstract: Rats spent 23h each day in a 1m2 octagonal arena with four pellet dispensers and 2 liquid-dispending bottles. During the water-only phase, both bottles were continuously available, and the location of the RI 60”, RI 120”, RI 180”, and RI 240” was varied in a counterbalanced sequence between feeders. Food schedules operated for 8 h or until rats received enough food to maintain their ad libitum weight. During the water-alcohol phase, one bottle dispensed a saccharin-sweetened 10% V/V solution of ethanol, while the location of the various RI schedules remained fixed; the location of the water and alcohol bottles alternated daily. Matching between the proportion of pellets obtained at a given feeder and the proportion of time spent in that area was systematically affected by the location of the water and alcohol bottles. While location of the water bottle was associated with higher than predicted time allocation, placement of the alcohol solution was associated with less time spent in that area. Daily alcohol consumption (˜ 6.0 gr/Kg) remained stable regardless of its location, and occurred almost exclusively during the time when the food schedules were inactive. Water consumption occurred at a steady rate during the feeding period with little or no drinking at other times. |
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| 42. A Three-Lever Drug Discrimination Procedure Differentiates GHB and Ethanol |
| Area: BPH; Domain: Basic Research |
| GABRIEL DANIEL SEARCY (Western Michigan University), Dori M. Pynnonen (Western Michigan University), Alan D. Poling (Western Michigan University), Lisa E. Baker (Western Michigan University) |
| Abstract: Recreational use and abuse of gamma-hydroxybutyrate (GHB) is becoming increasingly popular among adolescents and young adults. Although relatively little is known about the neurobehavioral effects of GHB, some reports indicate that this sedative produces effects similar to those of alcohol. However, previous studies comparing the discriminative stimulus effects of GHB to those of ethanol in rats indicate that these substances differ considerably, at least with respect to the mechanisms underlying their capacities to aquire stimulus control. To further explore the differences between GHB and ethanol, 8 male Sprague-Dawley rats were trained to discriminate orally-administered ethanol (1.0 g/kg) and GHB (300 mg/kg) from vehicle under a FR 10 schedule of food reinforcement in a three-lever drug discrimination. Seven animals met the discrimination criterion within 98.3 (± 8.3, range: 70-130) training sessions. Dose-response functions were determined with both training compounds. Additionally, as expected, the GHB precursors, GBL and 1, 4-BD produced full substitution for GHB. These results support previous findings that GHB and ethanol produce distinctly different discriminative stimulus effects. Substitution tests with the benzodiazepine, flunitrazepam and the GABAB agonist, baclofen are currently in progress. Stimulus antagonism tests are planned with the GABAB antagonist, CGP-35348 and the GHB antagonist, NCS 382. |
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| 43. Do Self-Reported Effects of Inhaled Anesthetics Predict Subsequent Self-Administration? |
| Area: BPH; Domain: Basic Research |
| ANDREW M. SYVERTSEN (University of Chicago), Diana J. Walker (University of Chicago) |
| Abstract: Self-reported (subjective) effects of drugs as well as their reinforcing effects are commonly used methods of assessing abuse liability of drugs in humans. It is widely believed that drugs function as reinforcers because of their subjective effects, and therefore the two measures should be highly correlated. We have not always found this to be the case. This ongoing study examines the relationship between subjective and reinforcing effects of the gaseous anesthetic, nitrous oxide (N2O), and a volatile anesthetic, sevoflurane. Previous studies found little correlation between ratings of N2O liking obtained while subjects were inhaling the drug and subsequent N2O choice, whereas sevoflurane results showed ratings of drug liking during drug inhalation did predict choice to some extent. This study tests whether a more comprehensive abuse liability assessment protocol might predict subsequent choice of inhaled anesthetic. We include several self-report measures indicative of abuse liability (i.e., putatively pleasant effects with face validity) and calculate a composite score of abuse liability-related subjective effects. Preliminary data for N2O show a positive correlation between ratings of drug liking and choice and between overall “abuse liability” scores and choice. Data will also be presented for sevoflurane, and we predict stronger correlations for the volatile anesthetic. |
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| 44. A Comparison Between Internet-Based Voucher Reinforcement and Nicotine Patches for Cigarette Smoking |
| Area: BPH; Domain: Applied Research |
| IRENE M. GLENN (University of Florida), Jesse Dallery (University of Florida) |
| Abstract: Abstinence reinforcement therapy is effective in promoting drug abstinence. Previously, we demonstrated the feasibility of an internet-based voucher reinforcement program for initiating smoking abstinence. In the current study we compared the efficacy of a 14-mg transdermal nicotine patch to vouchers contingent on smoking abstinence. Vouchers increased progressively in value, and a bonus voucher was delivered after every third consecutive negative sample. Abstinence was defined as a breath carbon monoxide (CO) level = 4 ppm. Participants were heavy smokers (> 20 cigs/day, at least a two year smoking history, and self-reported desire to quit). Two CO samples were obtained daily for both conditions. Participants recorded the sampling procedure in their home by using a web cam, and they emailed the video clip to research staff. The order of the two one-week experimental conditions (a patch and a voucher condition) was counterbalanced across participants. The voucher phase was more efficacious in initiating and maintaining abstinence than was the 14-mg transdermal nicotine patch. Supported by NIDA grant R21DA015289. |
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| 45. An Internet-Based Voucher Program for Smoking Abstinence |
| Area: BPH; Domain: Applied Research |
| STEVEN E. MEREDITH (University of Florida), Irene M. Glenn (University of Florida), Jesse Dallery (University of Florida) |
| Abstract: Abstinence reinforcement therapy is an effective treatment for promoting drug abstinence. Few studies, however, have extended this treatment to cigarette smokers. We exposed participants to an internet-based voucher program to initiate smoking abstinence. Participants were 20 heavy smokers (= 20 cigarettes/day for = 2 years and an initial carbon monoxide (CO) reading of = 20 ppm). The experiment consisted of an ABCDA design; wherein, A was a baseline phase in which participants earned non-contingent vouchers for submitting two samples daily, B was a shaping phase in which participants earned vouchers for reductions in CO values, C was an abstinence induction phase in which voucher value increased for each submission of a negative (= 7) CO value, and D was a thinning phase in which participants earned vouchers for only two negative readings. Participants were provided with a laptop, webcam, and CO monitor to record carbon monoxide levels twice each day (= 8 hours apart) for four weeks. Recordings were sent via email to researchers twice each day. Fifteen participants achieved sustained abstinence (CO = 7 ppm) during the abstinence induction phase. Results suggest internet-based abstinence reinforcement therapy is effective at promoting abstinence from cigarette smoking. Supported by NIDA grant R21DA015289. |
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