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| BPH Poster Session 4 |
| Monday, May 31, 2010 |
| 12:00 PM–1:30 PM |
| Exhibit Hall A (CC) |
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| 47. The Impact of Amphetamine on Resistance-to-Extinction Following Single-Schedule Training |
| Area: BPH; Domain: Experimental Analysis |
| STEPHEN H. ROBERTSON (James Madison Univeristy), Sherry L. Serdikoff (James Madison University) |
| Abstract: Some researchers have suggested that the discrepancy in findings between studies of resistance-to-extinction that use single-schedules and those that use multiple-schedules is the result of increased discriminability between training and extinction conditions in the single-schedule preparation, masking the true relation. Because amphetamine has been shown to interfere with stimulus control in a number of preparations, the current study examines the effects of amphetamine in the context of a single-schedule resistance-to-extinction preparation. During training, various doses of d-amphetamine and vehicle are administered 15-min prior to sessions where, water reinforcers are delivered according to various variable-interval schedules. The 50-min training sessions are conducted 5-7 days per week for each rat until responding is stable and are followed by a 2-hr extinction session. Resistance-to-extinction is represented as the logarithm (base 10) of the response rate for each extinction session as a proportion of the average response rate over the last 5 training sessions. To the extent that the data reveal a positive relation between resistance-to-extinction and reinforcer density during training when d-amphetamine but not vehicle is administered, they are consistent with the view that the discriminability between training and extinction is a confound that masks the true relation in single-schedule resistance-to-extinction procedures. |
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| 48. Effects of D-Amphetamine on Delay Discounting With Different Baselines |
| Area: BPH; Domain: Experimental Analysis |
| CHRISTOPHER KREBS (West Virginia University), Karen G. Anderson (West Virginia University) |
| Abstract: Impulsive choice is correlated with behavioral problems such as attention deficit hyperactivity disorder, substance abuse, and gambling. Variables such as reinforcer magnitude and delay have been shown to affect impulsive choice. Impulsive choice is often studied by presenting subjects with the choice between a smaller, more immediate and a larger, more delayed reinforcer. When a constant delay is added or subtracted to both alternatives, choice of the larger reinforcer has been found to increase or decrease, respectively. It is unknown if these effects generalize to within-session delay-discounting procedures where choice is between one food pellet delivered immediately and three food pellets delivered after an increasing delay. The present experiment examined how adding and subtracting a constant delay affects choice in eight male rats using a within-session delay-discounting procedure. As delay to the large reinforcer increased, choice for that option decreased in all rats regardless if a constant delay was added or subtracted. Indifference points were longer when constant delays were added and shorter when constant delays were subtracted from both alternatives. Thus, different baseline levels of choice were generated. Effects of acute d-amphetamine on choice at these different baselines were then assessed. |
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| 49. Does Continued Access Alter Economic Demand and Reinstatement? A Comparison of Methamphetamine and Food |
| Area: BPH; Domain: Experimental Analysis |
| Chad M. Galuska (College of Charleston), Kelly M. Banna (Medical University of South Carolina), LENA VAUGHN WILLSE (College of Charleston), Noushin Yahyavi-Firouz-Abadi (Medical University of South Carolina), Ronald E. See (Medical University of South Carolina) |
| Abstract: Prolonged use of psychostimulants may alter the essential value of the drug reinforcer, as well as a nondrug reinforcer such as food. To test this possibility, we trained rats to lever press in 2 hr daily sessions for methamphetamine (0.02 mg/50 ul) or a food pellet, both accompanied by a tone+light cue. A demand curve was first obtained by increasing the prevailing fixed-ratio (FR) response requirement across sessions. Subsequently, rats were given continued access to the reinforcer under an FR 3 schedule for 12 sessions. Additional control groups were not given continued access. Demand curves were then redetermined, followed by a minimum of 10 extinction sessions and a single cue-induced reinstatement test where responses produced only the tone+light. Continued access to food did not change its demand function. By comparison, methamphetamine consumption escalated with continued access. There was a tendency for the methamphetamine demand curve to shift upward (i.e., an increase in the initial level of demand) after continued access, but elasticity of demand did not change. Following extinction, levels of reinstatement were higher for methamphetamine than food, and highest in the rats that received continued access. |
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| 50. A Choice Reaction-Time Procedure for Assessing the Neurobehavioral Effects of Drugs and Toxicants With Rats |
| Area: BPH; Domain: Experimental Analysis |
| YUSUKE HAYASHI (National Institute for Occupational Safety and Health), James M. Antonini (National Institute for Occupational Safety and Health), Oliver Wirth (National Institute for Occupational Safety and Health) |
| Abstract: Four food-restricted Sprague-Dawley rats responded under a choice reaction-time (CRT) procedure. At the beginning of each trial, the rats were required to press a center lever for a variable duration of time to present a tone. The task then involved a conditional position discrimination in which a response to the left or right lever produced a food pellet intermittently following a high-pitched or low-pitched tone, respectively. Correct responses were reinforced with a probability of .95 or .05 under blinking or static houselights, respectively. After performance stabilized, effects of environmental, pharmacological, and toxicological variables were examined. First, rats were given free access to food 30 min prior to the session. Second, intensity of the tones was gradually decreased across sessions. Third, to affect neuromotor processes, rats were given a 0.03 mg/kg to 0.12 mg/kg intraperitoneal injection of haloperidol one hour prior to the session. Finally, to identify the behavioral effects of a repeated exposure to manual metal arc-hard surfacing (MMA-HS) welding fumes, the rats were exposed via intratracheal instillation to a 2.5-mg suspension of the welding fumes. Overall, the results provide evidence that the CRT procedure yields behavioral measures that are sensitive to changes in motivational, attentional, and/or motor processes. |
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| 51. Effects of Acute and Repeated Administration of Diazepam on Delay Discounting in Lewis and Fischer 344 Rats |
| Area: BPH; Domain: Experimental Analysis |
| SALLY HUSKINSON (West Virginia University), Amber Barse (West Virginia University), Karen G. Anderson (West Virginia University) |
| Abstract: Using a delay-discounting paradigm, impulsive choice is examined by providing subjects with a choice between two reinforcers of different magnitudes presented at varying delays. The larger delayed reinforcer is said to be devalued as a function of delay, and steeper discounting functions are indicative of more impulsive choices. Individual discounting rates can be influenced by many factors, including strain differences and drug effects. In the current experiment, choice was between one food pellet delivered immediately and three food pellets delivered after varying delays. Terminal delay values were functionally determined and equivalent in all rats as indicated by similar area under the curve values. Larger-reinforcer choice decreased as a function of increasing delays in all rats. Consistent with previous literature, Lewis rats emitted more impulsive choices as indicated by shorter indifference points than Fischer 344 rats. Effects of acute and repeated diazepam administration (1.0-5.6 mg/kg) were assessed in both strains and are discussed in terms of relative change from baseline (non-drug) conditions. Results from the present study may give insight into behavioral, neurochemical, and genetic determinants of impulsive choice. |
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| 52. Do Stimulant Medications for Attention Deficit Hyperactivity Disorder Enhance Learning? A Test of the Incremental Repeated Acquisition of Responses Procedure With Adults Who Benefit From Medication |
| Area: BPH; Domain: Experimental Analysis |
| DAVID M. TREJO (University of Wisconsin - Milwaukee), Marshall L. Dermer (University of Wisconsin - Milwaukee) |
| Abstract: There is no precise way to determine whether a person who is diagnosed with attention deficit hyperactivity disorder (ADHD) can better learn on than off stimulant medication. In the current study, three adults with ADHD, who clearly benefited from stimulant medication (Adderall/d and l- amphetamine or Ritalin/methylphenidate), were either on or off medication, for 30 sessions of an alternating treatments design, as they completed a learning task: the incremental repeated acquisition (IRA) procedure. IRA requires a participant to depress numeric keys in a given sequence to produce reinforcement. If a participant can press N keys correctly then he or she is required to next press N+1 keys. Importantly, from session-to session, the sequence varies. In this way the IRA procedure assesses learning. This research tested whether the IRA procedure was sensitive to the medication at the level of the individual participant. Various measures of learning were explored but only one measure, latency to complete a chain, appeared to be systematically affected by medication for one of three participants. Because the effect occurred during the later sessions, future researchers should consider conducting more sessions. More importantly, the IRA procedure’s sensitivity may be enhanced by conducting sessions that exceed 20 min. Although the procedure was rather insensitive to medication, visual inspection of the data, from session-to-session, often revealed smooth curves, despite the sequences changing, which suggest the IRA procedure is promising. |
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| 53. Discriminative Stimuli of Neuroactive Steroids and Benzodiazepines Are Similar but Not Identical in Rats |
| Area: BPH; Domain: Experimental Analysis |
| XIANG BAI (University of Texas Health Science Center at Austin), Lisa R. Gerak (University of Texas HSC-H) |
| Abstract: Neuroactive steroids and benzodiazepines are positive GABAA modulators with similar anxiolytic, sedative and anticonvulsant effects; however, their actions at different modulatory sites on GABAA receptors might confer differences in behavioral effects. This study compared the neuroactive steroid pregnanolone and the benzodiazepine midazolam to determine whether their effects can be differentiated using drug discrimination, a procedure with high pharmacological selectivity. Two groups of rats discriminated either 3.2 mg/kg pregnanolone or 0.56 mg/kg midazolam while responding under a fixed ratio 10 schedule of food presentation. Pregnanolone, midazolam and flunitrazepam produced greater than 80% drug-lever responding in both groups. Pregnanolone was more potent in rats discriminating pregnanolone, but the potencies of midazolam and flunitrazepam were not different between groups. Pentobarbital produced greater than 80% drug-lever responding in pregnanolone-discriminating rats and not in midazolam-discriminating rats. Ketamine and morphine produced little drug-lever responding in either group. Flumazenil antagonized midazolam and flunitrazepam, but not pregnanolone, in both groups. Despite many similarities between the pregnanolone and midazolam discriminative stimuli, two important differences were observed, suggesting that effects of positive GABAA modulators can be differentiated depending on their site of action. This study suggests that neuroactive steroids and benzodiazepines might vary in therapeutic profile. Supported by USPHS DA017240. |
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| 54. The Relative Contributions of Norepinephrine and Dopamine Transport Inhibition on Signal Detection in Rats |
| Area: BPH; Domain: Experimental Analysis |
| ELIZABETH C. FEIT (University of Wisconsin-Madison), Brenda L. McKee (University of Wisconsin-Madison), Sarah E. Eggenberger (University of Wisconsin-Madison) |
| Abstract: Attention-deficit/hyperactivity disorder (ADHD) is associated with a dysregulation of working memory, sustained attention and impulsivity/hyperactivity. Low doses of methylphenidate (MPH) are the most common and most effective pharmacotherapy for ADHD. In ADHD-affected individuals, low-dose stimulants reduce motor activity while improving performance in tests of working memory, sustained attention and impulsivity. Interestingly, the behavioral-enhancing and -calming actions of low-dose MPH are not limited to individuals with ADHD, but also extends to normal human and animal subjects. To better characterize the behavioral actions of low-dose psychostimulants, the present experiments examined the actions of MPH in a rat model of sustained attention, where signal and blank trials were interspersed randomly and occurred at unpredictable times. Consistent with previous observations, MPH affected sustained attention in a biphasic, inverted U function, improving attention at doses of 0.5 – 2.0 mg/kg and impairing attention at doses of 4.0 – 8.0 mg/kg. Surprisingly, neither norepinephrine nor dopamine transport inhibition, produced respectively with the drugs atomoxetine and GBR-12909 failed to replicate the effects of MPH. These data suggest that both NE and DA transport inhibition are required to improve attention in this model. |
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| 55. The Role of Dopamine in Time-Based and Effort-Based Optimal Foraging, Decision-Making Paradigms in Rats |
| Area: BPH; Domain: Experimental Analysis |
| BRENDA L. MCKEE (University of Wisconsin, Madison), Elizabeth C. Feit (University of Wisconsin-Madison), Sarah E. Eggenberger (University of Wisconsin-Madison) |
| Abstract: Optimal foraging theory holds that animals engage in behavioral strategies that maximize reinforcer procurement. Two “cost” variables exist when testing these theories in the laboratory, time and effort. We used a foraging simulation to test differences between effort and time requirements, and the role of dopamine in those variables. The simulation used a concurrent-chains arrangement and entailed repeated choices between two schedules of reinforcement: a progressive schedule (the “within-patch” or depleting patch option) and a fixed schedule (the “between patch” or traveling option). Furthermore, when an animal completed the fixed alternative (FR or FI), the progressive schedule (PR or PI) was reset to its minimum value. To test the effort, we employed ratio schedules (PR/FR); to test time we used interval schedules (PI/FI). Given these models’ unique ability to test time and effort and the importance of decision making in addiction, we tested amphetamine (0.5 mg/kg, i.p.) in rats trained in the PI/FI paradigm to best understand how systemic psychostimulant use alters time as an investment for reinforcement. Both the switch point and reinforcers earned were used as dependent variables. The optimal switch point on the PI/FI schedule, or the least amount of time to receive the most reinforcers, is for the rat to choose the PI lever on 4-5 consecutive choices, and then reset the PI by switching to the FI lever. Each rat was injected with saline or amphetamine every other day with the starting injection type randomized. Amphetamine failed to produce a statistically significant difference in the optimal switch point or reinforcers earned using a paired t-test. The role of systemic amphetamine in rats trained in the PR/FR paradigm is currently being tested. Although other models of effort-based decision making have delineated a role for dopamine, different dopamine D1 versus D2 receptor activation in this model has not been tested, nor has differential dopamine receptor modulation of time-based decision making been investigated. |
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| 56. Motivational and Attention Deficits in a Rat Model of Fetal Alcohol Syndrome |
| Area: BPH; Domain: Experimental Analysis |
| SARAH E. EGGENBERGER (University of Wisconsin-Madison), Echo Rufer (University of Wisconsin - Madison), Elizabeth C. Feit (University of Wisconsin-Madison), Brenda L. McKee (University of Wisconsin-Madison), Elliott M. Paletz (University of Wisconsin - Madison), Susan Smith (University of Wisconsin - Madison) |
| Abstract: Fetal alcohol syndrome disorder (FASD) is characterized by significant physical and behavioral problems. Children with FASD often have learning deficits, attention deficits, and exhibit impulsive patterns of behavior. While the primary cause of FASD is alcohol consumption during pregnancy, iron deficiency in the mother exacerbates these effects. We have recently developed a rat model of FASD combining alcohol exposure and iron deficiency. In this series of experiments, we attempted to validate this model using several standard operant behavior tasks. First, after rats were trained to lever-press, they were exposed to a session of a progressive ratio schedule of reinforcement. Interestingly, the iron deficient control group had a lower break point than the other groups. Second, all rats were then trained on a signal detection procedure, often considered an assay of sustained attention. Once again, the iron-deficient groups were deficient. This model, therefore, may provide scientists a useful paradigm for studying FASD, including possible pharmacological treatment of the disorder. |
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| 57. Alcohol-Reinforced Responding as a Function of Schedule and Rate of Reinforcement |
| Area: BPH; Domain: Experimental Analysis |
| AMY ELLERBE (University of Alaska Anchorage), Jennifer Lynnette LaCasse (University of Alaska Anchorage), Gwen Lupfer-Johnson (University of Alaska Anchorage), Eric S. Murphy (University of Alaska Anchorage) |
| Abstract: The present experiment tested the hypothesis that habituation to the reinforcer occurs during sessions of alcohol-reinforced responding in Long-Evans rats. Eight rats responded on fixed-interval (FI) and variable-interval (VI) schedules that provided programmed rates of reinforcement ranging from 60 to 450 reinforcers per 30 min session. In all conditions, reinforcers consisted of 3-s access to a 10% alcohol solution. Rates of responding were generally higher on the VI schedules than on FI schedules of the same value. Additionally, within-session decreases in responding were generally steeper during the FI than during the VI schedule that delivered the same rate of reinforcement. Neither the obtained rates of reinforcement, nor the self-administered dose of alcohol, differed between FI and VI schedules of the same value. These results are inconsistent with alternative hypotheses, such as “satiation” to the reinforcer and motor impairment. However, these findings are consistent with McSweeney, Murphy, and Kowal’s (2005) suggestion that habituation contributes to the regulation of drug-reinforced responding. |
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| 58. Absence of Learning and Memory Impairments in Female Rats Following Repeated Administration of Dextromethorphan During Adolescence |
| Area: BPH; Domain: Experimental Analysis |
| AMY DURGIN (Western Michigan University), Alan D. Poling (Western Michigan University) |
| Abstract: The present study investigated the effects of early repetitive exposure to dextromethorphan (DM), an N-methyl-D-aspartate (NMDA) receptor antagonist, on learning acquisition and working memory in female rats. Twenty-four female rats received 10 daily injections of DM (40 mg/kg) from postnatal day 28 through 37, and were then exposed to an eight-arm radial maze task at 2 and 6 months of age. Results showed no significant difference in performance between DM-treated and vehicle control rats for both tests. Although the current findings showed no enduring deleterious effects of DM, there have been a number of studies showing acute impairments in learning and memory following early exposure to this drug. Therefore, recreational abuse of DM early in life can be dangerous; however, further research examining the drug’s behavioral effects is warranted. |
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| 59. Effects of Alcohol Preload on Alcohol's Reinforcing Efficacy in College Students |
| Area: BPH; Domain: Applied Behavior Analysis |
| MEGAN B. BLACK (James Madison University), Sherry L. Serdikoff (James Madison University) |
| Abstract: This study examines whether college students find alcohol more reinforcing after receiving a priming dose (preload) of alcohol. In contrast to previous studies, this experiment uses the multiple choice procedure (MCP) to assess the reinforcing efficacy of alcohol preload. College students are given placebo or alcohol preloads. Thirty minutes after consuming the preload, participants complete a self-report measure to assess how much they crave alcohol as well as the multiple choice procedure (MCP). The MCP is an operant task on which participants make repeated choices between a pairs of reinforcers - alcohol or money - to assess the relative value of alcohol compared to money at that point in time. Choices are reinforced intermittently; following completion of the MCP, one of the choice options is chosen randomly and the reinforcer chosen for that pair or options is given to the participant. The current data add to the literature on this topic and extend current analyses by interpreting the findings within the conceptual framework of motivating operations where the value-altering effects of alcohol preload are operationalized as craving and the behavior-altering effects of alcohol preload are operationalized as MCP performance. |
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| 60. The Anitimalarial Mefloquine Does Not Share Discriminative Stimulus Properties With Uncompetitive NMDA Antagonists |
| Area: BPH; Domain: Experimental Analysis |
| RODNEY D. CLARK (Allegheny College), Emily Jutkiewicz (University of Michigan), James H. Woods (University of Michigan), Katy Orchowski (Allegheny College) |
| Abstract: Twelve male Sprague- Dawley rats were trained to discriminate both 1.78 mg/kg s.c. PCP and 1.78 mg/kg i.p. PCP from saline in a standard 2-response operant discrimination procedure consisting of two nose pokes. Responding was maintained under an FR-10 schedule of Ensure presentation. Substitution tests were conducted with PCP (1.0 – 5.6 mg/kg), Ketamine (1.0 – 10.0 mg/kg), MK-801 (.01 - .178 mg/kg), NMDA (10 – 30 mg/kg), and Mefloquine (3.0 – 10.0 mg/kg). Both ketamine and MK-801 produced dose-related PCP-appropriate responding while overall response rates for each drug were reduced in a dose-dependent manner. NMDA, however, did not produce any appreciable PCP-appropriate responding in any of the subjects tested at any of the doses tested. Moreover, response rates were reduced by nearly 50 percent. Mefloquine, when evaluated at doses ranging from 3.0 to 10.0 mg/kg did not engender any PCP-appropriate responding. These data suggest that while both PCP and Mefloquine may produce psychotic behavior, they apparently do so by different behavioral and pharmacological mechanisms. |
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