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| Using Behavioral Pharmacology to Investigate Factors That Alter Dopamine and Sensitivity to Reinforcement |
| Wednesday, November 15, 2017 |
| 10:30 AM–11:20 AM |
| Loft B, Niveau 3 |
| Area: BPN/EAB; Domain: Basic Research |
| Chair: Stephen H. Robertson (Idaho State University) |
| Abstract: Behavioral pharmacology is a sub-discipline of the Experimental Analysis of Behavior that combines operant and pharmacological techniques to better understand brain-behavior interactions. Mesolimbic dopamine neurotransmission has been implicated as a neural basis of reinforcement. As such, behavioral pharmacological procedures that utilize dopaminergic drugs can be used to investigate factors that influence sensitivity to reinforcement. This symposium will feature a series of talks that explore the interaction between developmental, neurotoxicological (methylmercury), dietary (high-fat, high-sugar diet), and genetic factors that lead to changes in sensitivity to dopaminergic drugs, which results in an altered sensitivity to delay- and effort-based reinforcement. These experiments offer further evidence that dopaminergic neurotransmission is a neural mechanism that underlies sensitivity to reinforcement, and disturbing dopamine signaling can produce long-lasting behavioral impairment. Generally, these studies illustrate the utility of using behavioral pharmacology techniques to identify and characterize the extent to which factors impact dopamine signaling and sensitivity to reinforcement. |
| Instruction Level: Intermediate |
| Keyword(s): Delay Discounting, Dopamine, Effort |
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| Haloperidol Unmasks Delay Discounting Effects in Rats Fed a High-Fat, High-Sugar Diet |
| STEPHEN H. ROBERTSON (Idaho State University), Erin B. Rasmussen (Idaho State University) |
| Abstract: Diet induced obesity (DIO) is a laboratory procedure in which rats are chronically exposed to a high-fat, high-sugar diet (i.e. cafeteria diet), which results in obesity, altered sensitivity to reward, and changes in the dopamine D2 system. In the current study, we exposed Sprague Dawley rats to a high-fat, high-sugar cafeteria-style diet or a standard rat chow diet for 8 weeks. Following the diet exposures, the rats were tested on a delay discounting task, in which preference for smaller, immediate vs. larger, delayed food outcomes were assessed. Once behavior was stable, acute administrations of haloperidol (0.03 0.1 mg/kg) commenced to assess the extent to which diet-induced changes in dopamine D2 influence impulsive food choice. Analyses revealed no baseline differences in percent larger, later choice as a function of diet; however, following an acute injection of 0.1 mg/kg of haloperidol, rats exposed to a high-fat, high-sugar diet showed a greater reduction in percent larger, later choice relative to rats fed a standard diet. As such, chronic exposure to a cafeteria-style diet alters dopamine signaling and results in an increased sensitivity to haloperidol that leads to increases in delay discounting relative to rats fed standard chow. |
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| Amphetamine and Methylmercury Exposure During Adolescence Alters Sensitivity to Monoamine Uptake Inhibitors in Adulthood |
| STEVEN R BOOMHOWER (Auburn University), M. Christopher Newland (Auburn University) |
| Abstract: Adolescent exposure to methylmercury (MeHg), an environmental neurotoxicant, may alter monoamine neurotransmission to change behavior in adulthood. Male C57Bl/6n mice were assigned to two MeHg- (0 ppm and 3 ppm) and two d-AMP-exposure groups (saline and 1 mg/kg), producing four treatment groups (n = 10-12/group): Control, MeHg, d-AMP, and MeHg + d-AMP. MeHg exposure spanned postnatal day 21 to 60 (murine adolescence), and once daily injections of d-AMP or saline spanned postnatal day 28 to 42. In adulthood, lever pressing was maintained under a multiple fixed-ratio (FR) schedule of reinforcement for milk (FR 1, 5, 15, 30, 60 and 120). Following baseline, acute i.p. injections of d-AMP (dopamine uptake inhibitor), desipramine (norepinephrine uptake inhibitor), and clomipramine (serotonin uptake inhibitor) were given. Responding was analyzed using Mathematical Principles of Reinforcement, a model whose parameters reveal information about motor function, reinforcer efficacy, and the effects of delayed reinforcement. Adolescent MeHg exposure decreased the number of responses coupled to reinforcement, and adolescent d-AMP administration reversed this effect. Adolescent amphetamine exposure increased sensitivity to acute d-AMP, and adolescent MeHg exposure prevented this effect. These data provide indirect evidence for the hypothesis that disruption of DA neurotransmission is a mechanism of MeHg-induced behavioral toxicity. |
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| The Interacting Roles of Genotype and Signaling Condition in Determining d-Amphetamine's Effects on Temporal Discounting: A Baseline-Dependent Account |
| DEREK POPE (Auburn University), M. Christopher Newland (Auburn University), Blake A. Hutsell (Virginia Commonwealth University) |
| Abstract: Amphetamine has been reported to increase or decrease preference for larger-delayed reinforcers depending on genotype, delay-progression, and signaling-conditions. To identify potential genotype X environment interactions responsible for these disparate findings, d-amphetamine's effects on delay discounting were assessed in two mouse-strains (BALB/c and C57Bl/6) responding under different stimulus conditions using a six-component, concurrent-chained schedule that randomized the within-session order of reinforcer delays. Across conditions, but within-subjects, components were presented without (mixed schedule) or with (multiple schedule) stimuli that signaled reinforcer delays and the effects of d-amphetamine were evaluated. Dose and schedule effects on generalized matching law magnitude and delay sensitivity were determined by a model-comparison approach. During baseline, magnitude and delay sensitivity were identical across stimulus conditions for BALB/cs and overall higher than the C57Bl/6s. For C57Bl/6s, magnitude and delay sensitivity were higher under the multiple than mixed schedule. Amphetamine decreased delay sensitivity under both schedules for BALB/cs, but this effect was attenuated by delay-specific stimuli. For C57Bl/6s, amphetamine decreased both magnitude and delay sensitivity under the multiple and increased each under the mixed schedule. Amphetamine decreased delay sensitivity when baseline levels were high and increased it when baseline levels were low, suggesting that effects were dependent upon baseline conditions. |
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