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| Behavioral and Pharmacological Mechanisms of Drug Action |
| Sunday, May 30, 2010 |
| 10:30 AM–11:50 AM |
| Travis C/D (Grand Hyatt) |
| Area: BPH; Domain: Experimental Analysis |
| Chair: Corina Jimenez-Gomez (University of Michigan) |
| Abstract: Behavioral pharmacology research primarily is concerned with the interplay of the pharmacological action of drugs and behavioral measures and methods. In this symposium, presentations will show a range of applications of various behavioral methods to inform about drug effects, as well as the use of pharmacological tools to learn more about behavioral processes. Hand and Reilly will present a study on the effects of stimulants and depressants on the microstructure of behavior through an IRT analysis. Ginsburg, Pinkston, and Lamb will present a study on the selectivity of the effects of serotonin reuptake inhibitor fluvoxamine on ethanol- vs. food-maintained responding. Aparicio, Lapointe, Hughes, and Pitts will present a study on the effects of raclopride and quinpirole, dopamine D2-like receptor ligands, on impulsive choices of Lewis and Fischer rats. Jimenez-Gomez, Winger, Woods, Dean, and Deaver will present a study on the effects of opioid-receptor antagonists on ethanol- and amphetamine-maintained responding in monkeys. These presentations represent current examples of the interplay of the fields of behavior analysis and pharmacology. |
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| Molecular Analyses of Drug Effects on Variable-Interval Responding in Pigeons |
| DENNIS J. HAND (Central Michigan University), Mark P. Reilly (Central Michigan University) |
| Abstract: Molar dependent measures, such as response rates for an entire session, are often compared between baseline and drug-probe sessions to quantify a drug’s effect on behavior. While useful at describing overall drug effects, such an analysis does not address the drug-induced moment-to-moment changes in responding which underlie response rate changes. Additionally, it is possible for overall response rates to remain unchanged while the distribution of responding within a session may be affected by a drug. Analyses of these molecular data may yield information regarding drug-induced behavioral variability and motivation to respond. Furthermore, molecular analyses may illuminate drug effects via differential sensitivity of certain classes of interresponse times (IRTs) (Bennett, Hughes & Pitts, 2007). Ongoing experiments are examining how CNS stimulants and depressants affect IRTs of multiple variable-interval (VI) 30-s, VI 60-s food-maintained responding by pigeons. Log-survivor analyses (Shull, Gaynor & Grimes, 2001) will be utilized to characterize the drug effects on IRTs. It is hypothesized that stimulants will increase the relative proportion of short IRTs while decreasing response-bout initiation. Depressants are hypothesized to decrease both bout initiation and the relative proportion of short IRTs. |
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| Selectivity of Fluvoxamine Effects on Ethanol-Maintained Behavior Depend on Schedule Conditions |
| BRETT C. GINSBURG (University of Texas HSC-H), Jonathan W. Pinkston (UT Health Science Center at San Antonio), R.J. Lamb (University of Texas HSC-H) |
| Abstract: Drugs that reduce ethanol-maintained behavior at lower doses or to a greater extent than another similar behavior are considered selective. Selective reduction of ethanol-maintained behavior may predict favorable therapeutic action and may identify neurochemical targets critical to ethanol reinforcement. In rats responding under a multiple fixed-ratio (FR5) schedule of food- and ethanol-maintained behavior with matched rates of responding and reinforcement, the selective serotonin reuptake inhibitor fluvoxamine selectively reduces responding for ethanol. In contrast, when responding for food and ethanol are maintained under a concurrent fixed-ratio schedule with matched rates of reinforcer delivery, fluvoxamine selectively reduces food-maintained behavior. Finally, when responding is maintained under a concurrent variable-interval schedule with similar rates of responding, fluvoxamine nonselectively reduces responding for both food and ethanol. These results demonstrate that the conditions under which behavior occurs can dramatically alter apparent selectivity of drug effects. Thus, results of experiments reporting such selective effects should be interpreted with caution and should be subjected to rigorous behavioral analysis before conclusions about the generality of the selectivity are drawn. |
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| Effects of Raclopride and Quinpirole in the Impulsive Choices of Lewis and Fischer 344 Rats |
| CARLOS F. APARICIO (The Aurora School), Kristine M. Lapointe (University of North Carolina, Wilmington), Christine E. Hughes (University of North Carolina, Wilmington), Raymond C. Pitts (University of North Carolina, Wilmington) |
| Abstract: Impulsivity is linked to insufficiencies of serotonin (5-HT) and dopamine (DA). Lewis rats are more impulsive than Fischer 344 rats. We assessed the possibility that this difference is related to activity at DA receptors by testing effects of the selective D2 agonist, quinpirole, and the selective D2 antagonist, raclopride, in Lewis and Fischer rats responding under a novel self-control procedure. Trials began by turning on the light above a back-wall lever, pressing that lever started the initial-link by inserting two front-levers. Pressing these levers gave access to the terminal links according to separate random-interval 10-s schedules. The terminal link for the left lever provided a smaller, sooner reinforcer (SSR) - 1 food pellet according to a fixed-interval (FI) 5-s schedule. The terminal link for the right lever provided a larger, later reinforcer (LLR) - 4 food-pellets according to FIs of 5, 10, 20, 40 or 80 s. The FI associated with the LLR varied randomly within each session across blocks of trials. Quinpirole decreased slopes of the delay-discount functions for both Lewis and Fischer rats, indicating that both rat strains became more self-controlled. Raclopride decreased slopes of the discount functions for the Fischer, but not for the Lewis rats. |
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| Decreasing the Reinforcing Effects of Intravenous Ethanol and Amphetamine in Rhesus Monkeys With Opioid Antagonists |
| CORINA JIMENEZ-GOMEZ (University of Michigan), Gail Winger (University of Michigan), James H. Woods (University of Michigan), Reginald L. Dean (Alkermes, Inc.), Daniel R. Deaver (Alkermes, Inc.) |
| Abstract: Drug abuse treatment has generally focused on the use of agonists (e.g., methadone) that activate the same receptors that are activated by the particular drug of abuse (e.g., heroin). Although this approach has proven useful in the clinic, it may be limited due to the addictive properties of the treatment drugs themselves. Antagonist therapy would avoid this and other drawbacks of agonist therapy. The opioid antagonist naltrexone is effective in reducing use of heroin in detoxified, compliant individuals, and alcohol abuse. RDC-5768 is a member of a family of novel opioid antagonists designed for increased metabolic stability compared to orally administered naltrexone. The purpose of this study was to assess the effects of RDC-5768 on ethanol and d-amphetamine self-administration in rhesus monkeys. Monkeys were trained to respond for intravenous injections of either ethanol or amphetamine on a fixed-ratio 30 time-out 10-s schedule. RDC-5768 or naltrexone was administered intramuscularly 30 minutes prior to the start of test sessions. RDC-5768 dose-dependently decreased both ethanol and d-amphetamine self-administration. In addition, naltrexone (a positive control) decreased ethanol self-administration. These findings support the potential use of opioid antagonists as therapy for psychostimulant abuse, and could potentially be useful for the treatment of polydrug abuse. |
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