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A novel IV cocaine self-administration procedure in rats: differential effects of dopamine, serotonin, and GABA drug pre-treatments on cocaine consumption and maximal price paid

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Abstract

Rationale

Behavior occurring during cocaine self-administration can be classified as either consummatory or appetitive. These two concepts are usually addressed independently using separate reinforcement schedules. For example, appetitive behavior can be assessed with a progressive ratio schedule, whereas consummatory behavior is typically measured using a fixed ratio schedule.

Objectives

Depending on the schedule used, it is often difficult to determine whether a particular drug pretreatment is affecting self-administration through an effect on appetitive responding, consummatory responding, or perhaps both. In the present study, we tested the effect of pretreating rats with four different drugs on appetitive and consummatory behaviors.

Materials and methods

We recently developed a technique that provides an independent assessment of both behavioral concepts within the same experimental session. In this threshold procedure, rats are offered a descending series of 11 unit doses (422–1.3 μg/injection) during consecutive timed intervals under a fixed-ratio schedule. Consummatory behavior can be analyzed by assessing intake at high unit doses; an estimate of appetitive responding can be determined from responding occurring at the threshold dose. Applying behavioral economics to these data provides dependent measures of consumption when minimally constrained by price and the maximal price paid (P max) for cocaine.

Results

Haloperidol increased cocaine consumption when minimally constrained by price but decreased P max. In contrast, d-amphetamine increased P max. Fluoxetine decreased P max and consumption when minimally constrained by price. Baclofen selectively decreased P max.

Conclusions

These data suggest that drug pretreatments can alter consummatory and appetitive behavior differently because each concept involves distinct neural mechanisms.

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Acknowledgments

Funding for this study was provided by grants R01DA14030 (DCSR) and F31DA024525 (EBO). We would like to thank Leanne N. Thomas for technical assistance and Benjamin Zimmer for helpful comments in the preparation of this manuscript. We would especially like to thank Dr. Steve Hursh for providing spreadsheets and mathematical equations that aided in the mathematical behavioral economic analyses.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA

    Erik B. Oleson & David C. S. Roberts

  2. Winston-Salem State University, Winston-Salem, NC, 27110, USA

    Jasmine M. Richardson

  3. Department of Neurobiology and Anatomy, University of Maryland School of Medicine, 20 Penn St., Baltimore, MD, 21201, USA

    Erik B. Oleson

Authors
  1. Erik B. Oleson
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  2. Jasmine M. Richardson
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  3. David C. S. Roberts
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Corresponding author

Correspondence to Erik B. Oleson.

Electronic supplementary material

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Supplementary Figure 1

Demand curves are shown for individual rats treated with vehicle (right, open circles) and during baseline responding (left, filled circles). P max values were calculated graphically (gP max) as described in the methods and using an equation (cP max). To assess P max mathematically, each animal’s price intake data were curve-fit using the equation: \( { \log }(Q) = { \log }\left( {{Q_0}} \right) + k \times \left( {{e^{{ - \alpha \times {Q_0} \times C}}} - 1} \right) \). Mathematically calculated P max (cP max) was determined to be the unit price at which the first derivative point slope of the function = −1. Q 0, which represents initial consumption at minimal price, and α, which represents the acceleration of the function in response to changes in price, were manipulated to achieve best fit (R 2). Consumption at minimal price was also calculated as an average of cocaine intake across bins 2–4 of the threshold procedure. The value k, which represents the range of consumption in logarithmic units, was set to 2 for all animals. It should be noted that the dependent measures of the maximal price paid (gP max and cP max) are highly correlated, as are the dependent measures of consumption at minimal price (Cons and Q 0; see ESM Figs. S5 and 6 for correlations; see Hursh and Silberberg 2008 for a complete description of this mathematical approach) (DOC 177 kb)

Supplementary Figure 2

Demand curves are shown for individual rats treated with vehicle (right, open circles) and during baseline responding (left, filled circles). P max values were calculated graphically (gP max) as described in “Materials and methods” and using an equation (cP max). To assess P max mathematically, each animal’s price intake data were curve-fit using the equation: \( { \log }(Q) = { \log }\left( {{Q_0}} \right) + k \times \left( {{e^{{ - \alpha \times {Q_0} \times C}}} - 1} \right) \). Mathematically calculated P max (cP max) was determined to be the unit price at which the first derivative point slope of the function = −1. Q0, which represents initial consumption at minimal price, and α, which represents the acceleration of the function in response to changes in price, were manipulated to achieve best fit (R 2). Consumption at minimal price was also calculated as an average of cocaine intake across bins 2–4 of the threshold procedure. The value k, which represents the range of consumption in logarithmic units, was set to 2 for all animals. It should be noted that the dependent measures of the maximal price paid (gP max and cP max) are highly correlated, as are the dependent measures of consumption at minimal price (Cons and Q 0; see ESm Figs. S5 and 6 for correlations; see Hursh and Silberberg 2008 for a complete description of this mathematical approach) (DOC 177 kb)

Supplementary Figure 3

Demand curves are shown for individual rats treated with vehicle (right, open circles) and during baseline responding (left, filled circles). P max values were calculated graphically (gP max) as described in “Materials and methods” and using an equation (cP max). To assess P max mathematically, each animal’s price intake data were curve-fit using the equation: \( { \log }(Q) = { \log }\left( {{Q_0}} \right) + k \times \left( {{e^{{ - \alpha \times {Q_0} \times C}}} - 1} \right) \). Mathematically calculated P max (cP max) was determined to be the unit price at which the first derivative point slope of the function = −1. Q 0, which represents initial consumption at minimal price, and α, which represents the acceleration of the function in response to changes in price, were manipulated to achieve best fit (R 2). Consumption at minimal price was also calculated as an average of cocaine intake across bins 2–4 of the threshold procedure. The value k, which represents the range of consumption in logarithmic units, was set to 2 for all animals. It should be noted that the dependent measures of the maximal price paid (gP max and cP max) are highly correlated, as are the dependent measures of consumption at minimal price (Cons and Q 0; see ESM Figs. S5 and 6 for correlations; see Hursh and Silberberg 2008 for a complete description of this mathematical approach) (DOC 172 kb)

Supplementary Figure 4

Demand curves are shown for individual rats treated with vehicle (right, open circles) and during baseline responding (left, filled circles). P max values were calculated graphically (gP max) as described in the methods and using an equation (cP max). To assess P max mathematically, each animal’s price intake data were curve-fit using the equation: \( { \log }(Q) = { \log }\left( {{Q_0}} \right) + k \times \left( {{e^{{ - \alpha \times {Q_0} \times C}}} - 1} \right) \). Mathematically calculated P max (cP max) was determined to be the unit price at which the first derivative point slope of the function = −1. Q 0, which represents initial consumption at minimal price, and α, which represents the acceleration of the function in response to changes in price, were manipulated to achieve best fit (R 2). Consumption at minimal price was also calculated as an average of cocaine intake across bins 2–4 of the threshold procedure. The value k, which represents the range of consumption in logarithmic units, was set to 2 for all animals. It should be noted that the dependent measures of the maximal price paid (gP max and cP max) are highly correlated, as are the dependent measures of consumption at minimal price (Cons and Q 0; see ESM Figs. S5 and 6 for correlations; see Hursh and Silberberg 2008 for a complete description of this mathematical approach) (DOC 134 kb)

Supplementary Figure 5

Measures of consummatory behavior are not related to measures of appetitive behavior (TIFF 8222 kb)

Supplementary Figure 6

The dependent measure of consummatory behavior determined by averaging intake across bins 2-4 (Cons) correlates highly with a mathematically derived value of consumption at minimal price (Q0) (TIFF 8222 kb)

Supplementary Figure 7

Graphically determined Pmax (gPmax) correlates highly with mathematically calculated Pmax (cPmax) (TIFF 8222 kb)

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Oleson, E.B., Richardson, J.M. & Roberts, D.C.S. A novel IV cocaine self-administration procedure in rats: differential effects of dopamine, serotonin, and GABA drug pre-treatments on cocaine consumption and maximal price paid. Psychopharmacology 214, 567–577 (2011). https://doi.org/10.1007/s00213-010-2058-6

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