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Diazepam blocks 50 kHz ultrasonic vocalizations and stereotypies but not the increase in locomotor activity induced in rats by amphetamine

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Abstract

Rationale

We have recently shown that the benzodiazepine diazepam inhibits dopamine release in the NAc and blocks the increased release of dopamine induced by DL-amphetamine. Rewarding stimuli and many drugs of abuse can induce dopamine release in the nucleus accumbens as well as 50-kHz ultrasonic vocalizations (USVs) in rats.

Objectives

In the present study, we tested the hypothesis that diazepam can also block the increase in locomotor activity and USVs elicited by amphetamine.

Methods

Fifty-kilohertz USVs, stereotypy, and locomotor behavior were scored in adult male Wistar rats treated with i.p. injections of saline, 3 mg/kg DL-amphetamine, 2 mg/kg diazepam, 0.2 mg/kg haloperidol, or a combination of these drugs.

Results

In agreement with previous studies, amphetamine caused significant increases in the number of USV calls, stereotypies, and locomotor activity. The D2 dopamine receptor antagonist haloperidol blocked the effects of amphetamine on USVs, stereotypy, and locomotor activity. Diazepam blocked the effect of amphetamine on USV and stereotypy, but not on horizontal locomotion.

Conclusions

These results suggest that diazepam blocks the rewarding effect of amphetamine. This finding is promising for basic research regarding treatments of substance use disorders and evaluation of the impact of benzodiazepines on motivation.

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Contributors

C.D.C, R.A., D.L.R., and R.K.W.S. designed the research; G.O.G. and D.D.V performed the research; G.O.G., C.D.C, D.D.V. D.L.R., and R.A. analyzed the data; and G.O.G. and C.D.C wrote the paper.

Role of the funding source

GOG, DDV, RA, and CDC were supported by INNT, CNPq, CAPES, and UFPR; SCHW was supported by DFG (SCHW 559/14–1); and DLR was supported by the UNC Bowles Center for Alcohol Studies.

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Authors and Affiliations

  1. Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, 81.530-980, Brazil

    Gisele de Oliveira Guaita, Debora Dalla Vecchia, Roberto Andreatini & Claudio Da Cunha

  2. Department of Psychiatry and Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, 27599-7178, USA

    Donita L. Robinson

  3. Behavioral Neuroscience, Experimental and Biological Psychology, Faculty of Psychology, Marburg Center for Mind, Brain and Behavior (MCMBB), Philipps-University of Marburg, 35032, Marburg, Germany

    Rainer K. W. Schwarting

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  1. Gisele de Oliveira Guaita
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  2. Debora Dalla Vecchia
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  3. Roberto Andreatini
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  4. Donita L. Robinson
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  5. Rainer K. W. Schwarting
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  6. Claudio Da Cunha
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Correspondence to Claudio Da Cunha.

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de Oliveira Guaita, G., Vecchia, D.D., Andreatini, R. et al. Diazepam blocks 50 kHz ultrasonic vocalizations and stereotypies but not the increase in locomotor activity induced in rats by amphetamine. Psychopharmacology 235, 1887–1896 (2018). https://doi.org/10.1007/s00213-018-4878-8

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