|
| Using Laboratory Models to Identify Therapeutic and Detrimental Effects of Drugs |
| Sunday, May 24, 2015 |
| 4:00 PM–4:50 PM |
| 008A (CC) |
| Area: BPH/EAB; Domain: Basic Research |
| Chair: David R. Maguire (University of Texas Health Science Center at San Antonio) |
| Abstract: Drugs are widely used, both therapeutically and recreationally. Assessment of the therapeutic and detrimental effects of drugs, for the purposes of both developing effective medications and understanding drug addiction, has relied heavily on research in behavioral pharmacology and the development of a sophisticated science of behavior. This symposium covers several lines of research from different laboratories assessing the behavioral effects of drugs using laboratory models. The first presenter (Kangas) examines effects of daily methamphetamine self-administration on learning and cognitive flexibility in squirrel monkeys. The second presenter (Soto) compares the effects of current and potential medications for attention-deficit/hyperactivity disorder on delay discounting in rats. The third presenter (Maguire) discusses interactions between the therapeutic and abuse-related effects cannabinoids (e.g., Δ9-tetrahydrocannabinol) and opioids (e.g., morphine) in rhesus monkeys. Taken together, these presentations will provide a sampling of current research in behavioral pharmacology. Moreover, they will highlight the complex interactions among drugs, behavior, and environment and will underscore the importance of behavioral pharmacology for the assessment of therapeutic and detrimental effects of drugs. |
| Keyword(s): abuse, drugs, preclinical, therapeutics |
| |
| Effects of Self-Administered Methamphetamine on Discrimination Learning and Reversal in the Monkey |
| BRIAN D. KANGAS (Harvard Medical School) |
| Abstract: Worldwide use of amphetamines exceeds that of heroin and cocaine combined and the illicit use of methamphetamine presents a global health challenge. Chronic exposure to methamphetamine has profound neural impact that may be related to adverse effects on learning. The present study assessed the effects of daily intravenous methamphetamine self-administration on touchscreen-based models of learning in monkeys. Subjects engaged in a repeated acquisition task in which the rate of discrimination learning was assessed over time. Subsequently, the discrimination reversal task was introduced requiring subjects to inhibit a previously reinforced response and respond to the initially ineffective stimulus to obtain reinforcement. Time course between self-administration and touchscreen session was also evaluated. Results indicated that daily methamphetamine self-administration produced markedly deleterious effects on the development of discrimination learning. Importantly, the magnitude of adverse effects was highly correlated with the level of daily methamphetamine intake among individual subjects. Discrimination reversal was largely unaffected. However, when the interval between self-administration and the touchscreen session was reduced, reversal performance was more vulnerable to the direct effects of methamphetamine. These results indicate that methamphetamine can have dramatic deleterious effects on learning and highlights interesting differences between its direct acute effects and the consequences of chronic exposure. |
| |
| Effects of Benztropine Analogs on Delay Discounting in Rats |
| PAUL L. SOTO (Texas Tech University), Amy Newman (National Institute on Drug Abuse), Jonathan L. Katz (National Institute on Drug Abuse) |
| Abstract: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent behavioral disorder characterized by symptoms of inattention, impulsivity, and hyperactivity. In the laboratory, discounting the effectiveness of delayed reinforcers is used to study impulsivity. Delay-discounting refers to the tendency to select small-immediate over larger-delayed reinforcers. The current study evaluated effects on discounting of therapeutic standards, methlyphenidate (MPH) and d-amphetamine (d-AMPH), cocaine, as well as several benztropine analogs (AHN1055, AHN2005, JHW007). During sessions, completion of five responses by rats on one lever produced one pellet immediately or if on the other lever four pellets after a delay. The delay to the four pellets varied across blocks of trials within sessions in either an ascending order, or in another group in a random order. Baseline rates of discounting were higher in the Ascending-Order compared to Random-Order subjects. d-AMPH and MPH dose-dependently decreased or showed a trend to decrease discounting in both groups. Cocaine was without consistent effects on discounting. AHN1055 decreased discounting in both groups. In contrast, AHN2005 and JHW007 did not produce consistent effects on discounting in either group. Results indicate that presentation order can affect discounting, and that this preclinical procedure predicts therapeutic effects of AHN 1055 like those of the clinical standards. |
| |
| Interactions Between the Discriminative Stimulus Effects of Mu Opioid Receptor Agonists and Cannabinoid Receptor Agonists |
| DAVID R. MAGUIRE (University of Texas Health Science Center at San Antonio), Charles Patrick France (University of Texas Health Science Center at San Antonio) |
| Abstract: Cannabinoids such as Δ9-tetrahydrocannabinol (THC) enhance some (antinociceptive) but not other (e.g., discriminative stimulus) effects of opioids, suggesting that cannabinoids can be combined with opioids to treat pain without also increasing abuse. Cannabinoids more effectively enhance the antinociceptive effects of drugs with high efficacy at the mu opioid receptor as compared with those having lower efficacy. Whether efficacy impacts the interactions between other effects of opioids and cannabinoids is unknown. This study examined whether the cannabinoid receptor agonists THC and CP55940 differentially impact the discriminative stimulus effects of agonists varying in efficacy at the mu opioid receptor. In monkeys discriminating the mu opioid receptor agonist fentanyl, etorphine and nalbuphine dose-dependently increased drug-lever responding. Smaller doses of THC and CP55940 were required to shift the nalbuphine dose-effect curve rightward as compared with those required to shift the fentanyl or etorphine curves. These data indicate that the discriminative stimulus effects of the lower efficacy drug nalbuphine are more easily attenuated than those of the higher efficacy drugs fentanyl and etorphine. That the discriminative stimulus effects of some drugs are more susceptible to attenuation than others might have implications for assessing abuse liability of drug combinations, especially if combinations have therapeutic potential. |
|
| |