Diazepam blocks 50 kHz ultrasonic vocalizations and stereotypies but not the increase in locomotor activity induced in rats by amphetamine
- 73 Downloads
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.
In the present study, we tested the hypothesis that diazepam can also block the increase in locomotor activity and USVs elicited by amphetamine.
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.
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.
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.
KeywordsDiazepam Amphetamine Dopamine Addiction Drugs of abuse Psychostimulants
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Burgdorf J, Kroes RA, Moskal JR, Pfaus JG, Brudzynski SM, Panksepp J (2008) Ultrasonic vocalizations of rats (Rattus norvegicus) during mating, play, and aggression: behavioral concomitants, relationship to reward, and self-administration of playback. J Comp Psychol 122:357–367CrossRefPubMedGoogle Scholar
- Kablinger AS, Lindner MA, Casso S, Hefti F, DeMuth G, Fox BS, McNair LA, McCarthy BG, Goeders NE (2012) Effects of the combination of metyrapone and oxazepam on cocaine craving and cocaine taking: a double-blind, randomized, placebo-controlled pilot study. J Psychopharmacol 26:973–981CrossRefPubMedGoogle Scholar
- Kuczenski R, Segal DS, Aizenstein ML (1991) Amphetamine, cocaine, and fencamfamine -relationship between locmotor and stereotypy response profiles and caudate and accumbens-dopamine dynamics. J Neurosci 11:2703–2712Google Scholar
- Ringel LE, Basken JN, Grant LM, Ciucci MR (2013) Dopamine D1 and D2 receptor antagonism effects on rat ultrasonic vocalizations. Behav Brain Res 252-259Google Scholar
- Sams-Dodd F (1998) Effects of continuous D-amphetamine and phencyclidine administration on social behaviour, stereotyped behaviour, and locomotor activity in rats. Neuropsychopharmacol 19:18–25Google Scholar
- Schwarting RKW, Natusch C, Llano L, Bedenk B, Borchers M, Wohr M (2007a) 50-kHz ultrasonic calling in male rats: environmental, social and subjective factors. Behav Pharmacol 18:S66–S67Google Scholar
- Simola N (2015) Rat Ultrasonic Vocalizations and Behavioral Neuropharmacology: From the Screening of Drugs to the Study of Disease. Current Neuropharmacology 13:164–179Google Scholar
- Simola N, Frau L, Plumitallo A, Morelli M (2014) Direct and long lasting effects elicited by repeated drug administration on 50-kHz ultrasonic vocalizations are regulated differently: implications for the study of the affective properties of drugs of abuse. Int J Neuropsychopharmacol 17:429–441CrossRefPubMedGoogle Scholar
- Wendler E, De Souza CP, Vecchia DD, Kanazawa LKS, Soares d A, Hocayen P, Wöhr M, Schwarting RKW, Andreatini R (2016) Evaluation of 50-kHz ultrasonic vocalizations in animal models of mania: ketamine and lisdexamfetamine-induced hyperlocomotion in rats. Eur Neuropsychopharmacol 26:1900–1908CrossRefPubMedGoogle Scholar