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The self-administration of rapidly delivered cocaine promotes increased motivation to take the drug: contributions of prior levels of operant responding and cocaine intake

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Abstract

Rationale

Rapid drug delivery to the brain might increase the risk for developing addiction. In rats, increasing the speed of intravenous cocaine delivery (5 vs. 90 s) increases drug intake and the subsequent motivation to self-administer cocaine. Increased motivation for cocaine could result not only from more extensive prior drug intake and operant responding for drug, but also from neuroplasticity evoked by rapid drug uptake.

Objective

We determined the contributions of prior drug intake and operant responding to the increased motivation for cocaine evoked by rapid delivery. We also investigated the effects of cocaine delivery speed on corticostriatal expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) mRNA.

Methods

Rats self-administered cocaine (0.25 mg/kg/infusion) delivered over 5 or 90 s during short-access (1 h/session; ShA) or long-access (6 h; LgA) sessions. Motivation for cocaine was then assessed by measuring responding under a progressive ratio schedule of reinforcement. Next, BDNF and TrkB mRNA levels were measured in 5- and 90-s rats.

Results

Five-second ShA and 5-s-LgA rats were more motivated for cocaine than their 90-s counterparts. This effect was dissociable from previous levels of drug intake or of operant responding for cocaine. In parallel, only rats self-administering rapid cocaine injections had altered BDNF and TrkB mRNA levels in corticostriatal regions.

Conclusions

Rapid drug delivery augments the motivation for cocaine independently of effects on the levels of drug intake or operant responding for drug. We suggest that rapid delivery might increase the motivation for drug by promoting neuroplasticity within reward pathways. This neuroplasticity could involve increased regulation of BDNF/TrkB.

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Acknowledgments

We are indebted to M. David Voyer for technical assistance with the in situ hybridization assays. This research was supported by an operating grant from the Canadian Institutes of Health Research (http://www.cihr-irsc.gc.ca/e/193.html) to ANS (Grant No. 97841) and an infrastructure grant from the Canada Foundation for Innovation (http://www.innovation.ca/en) to ANS (Grant No. 24326). ANS holds a salary award (Grant No. 16193) and KBG holds a Masters fellowship (Grant No. 25237), both from the Fonds de la Recherche en Santé du Québec (http://www.frsq.gouv.qc.ca/en/index.shtml). EAM holds a doctoral fellowship from the Université de Montréal’s Groupe de recherche sur le système nerveux central.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, QC, H3C 3J7, Canada

    Karim Bouayad-Gervais, Ellie-Anna Minogianis & Anne-Noël Samaha

  2. Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada

    Daniel Lévesque

  3. CNS Research Group, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada

    Daniel Lévesque & Anne-Noël Samaha

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  1. Karim Bouayad-Gervais
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  2. Ellie-Anna Minogianis
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  3. Daniel Lévesque
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  4. Anne-Noël Samaha
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Correspondence to Anne-Noël Samaha.

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Karim Bouayad-Gervais and Ellie-Anna Minogianis contributed equally to the work presented here.

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Bouayad-Gervais, K., Minogianis, EA., Lévesque, D. et al. The self-administration of rapidly delivered cocaine promotes increased motivation to take the drug: contributions of prior levels of operant responding and cocaine intake. Psychopharmacology 231, 4241–4252 (2014). https://doi.org/10.1007/s00213-014-3576-4

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