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Increased amphetamine-induced locomotor activity, sensitization, and accumbal dopamine release in M5 muscarinic receptor knockout mice

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Harvard

Schmidt, LS, Miller, AD, Lester, DB, Bay-Richter, C, Schülein, C, Frikke-Schmidt, H, Wess, J, Blaha, CD, Woldbye, DPD, Fink-Jensen, A & Wörtwein, G 2009, 'Increased amphetamine-induced locomotor activity, sensitization, and accumbal dopamine release in M5 muscarinic receptor knockout mice' Psychopharmacology, vol. 207, no. 4, pp. 547-58. https://doi.org/10.1007/s00213-009-1685-2

APA

CBE

Schmidt LS, Miller AD, Lester DB, Bay-Richter C, Schülein C, Frikke-Schmidt H, Wess J, Blaha CD, Woldbye DPD, Fink-Jensen A, Wörtwein G. 2009. Increased amphetamine-induced locomotor activity, sensitization, and accumbal dopamine release in M5 muscarinic receptor knockout mice. Psychopharmacology. 207(4):547-58. https://doi.org/10.1007/s00213-009-1685-2

MLA

Vancouver

Author

Schmidt, Lene S ; Miller, Anthony D ; Lester, Deranda B ; Bay-Richter, Cecilie ; Schülein, Christina ; Frikke-Schmidt, Henriette ; Wess, Jürgen ; Blaha, Charles D ; Woldbye, David P D ; Fink-Jensen, Anders ; Wörtwein, Gitta. / Increased amphetamine-induced locomotor activity, sensitization, and accumbal dopamine release in M5 muscarinic receptor knockout mice. In: Psychopharmacology. 2009 ; Vol. 207, No. 4. pp. 547-58.

Bibtex

@article{f255bdd03f3b11dfa3b3000ea68e967b,
title = "Increased amphetamine-induced locomotor activity, sensitization, and accumbal dopamine release in M5 muscarinic receptor knockout mice",
abstract = "INTRODUCTION: Muscarinic M(5) receptors are the only muscarinic receptor subtype expressed by dopamine-containing neurons of the ventral tegmental area. These cells play an important role for the reinforcing properties of psychostimulants and M(5) receptors modulate their activity. Previous studies showed that M(5) receptor knockout (M (5) (-/-) ) mice are less sensitive to the reinforcing properties of addictive drugs. MATERIALS AND METHODS: Here, we investigate the role of M(5) receptors in the effects of amphetamine and cocaine on locomotor activity, locomotor sensitization, and dopamine release using M (5) (-/-) mice backcrossed to the C57BL/6NTac strain. STATISTICAL ANALYSES: Sensitization of the locomotor response is considered a model for chronic adaptations to repeated substance exposure, which might be related to drug craving and relapse. The effects of amphetamine on locomotor activity and locomotor sensitization were enhanced in M (5) (-/-) mice, while the effects of cocaine were similar in M (5) (-/-) and wild-type mice. RESULTS: Consistent with the behavioral results, amphetamine-, but not cocaine, -elicited dopamine release in nucleus accumbens was enhanced in M (5) (-/-) mice. DISCUSSION: The different effects of amphetamine and cocaine in M (5) (-/-) mice may be due to the divergent pharmacological profile of the two drugs, where amphetamine, but not cocaine, is able to release intracellular stores of dopamine. In conclusion, we show here for the first time that amphetamine-induced hyperactivity and dopamine release as well as amphetamine sensitization are enhanced in mice lacking the M(5) receptor. These results support the concept that the M(5) receptor modulates effects of addictive drugs.",
author = "Schmidt, {Lene S} and Miller, {Anthony D} and Lester, {Deranda B} and Cecilie Bay-Richter and Christina Sch{\"u}lein and Henriette Frikke-Schmidt and J{\"u}rgen Wess and Blaha, {Charles D} and Woldbye, {David P D} and Anders Fink-Jensen and Gitta W{\"o}rtwein",
note = "Keywords: Amphetamine; Animals; Cocaine; Dopamine; Dopamine Uptake Inhibitors; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Nucleus Accumbens; Receptor, Muscarinic M5",
year = "2009",
doi = "10.1007/s00213-009-1685-2",
language = "English",
volume = "207",
pages = "547--58",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer",
number = "4",

}

RIS

TY - JOUR

T1 - Increased amphetamine-induced locomotor activity, sensitization, and accumbal dopamine release in M5 muscarinic receptor knockout mice

AU - Schmidt, Lene S

AU - Miller, Anthony D

AU - Lester, Deranda B

AU - Bay-Richter, Cecilie

AU - Schülein, Christina

AU - Frikke-Schmidt, Henriette

AU - Wess, Jürgen

AU - Blaha, Charles D

AU - Woldbye, David P D

AU - Fink-Jensen, Anders

AU - Wörtwein, Gitta

N1 - Keywords: Amphetamine; Animals; Cocaine; Dopamine; Dopamine Uptake Inhibitors; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Nucleus Accumbens; Receptor, Muscarinic M5

PY - 2009

Y1 - 2009

N2 - INTRODUCTION: Muscarinic M(5) receptors are the only muscarinic receptor subtype expressed by dopamine-containing neurons of the ventral tegmental area. These cells play an important role for the reinforcing properties of psychostimulants and M(5) receptors modulate their activity. Previous studies showed that M(5) receptor knockout (M (5) (-/-) ) mice are less sensitive to the reinforcing properties of addictive drugs. MATERIALS AND METHODS: Here, we investigate the role of M(5) receptors in the effects of amphetamine and cocaine on locomotor activity, locomotor sensitization, and dopamine release using M (5) (-/-) mice backcrossed to the C57BL/6NTac strain. STATISTICAL ANALYSES: Sensitization of the locomotor response is considered a model for chronic adaptations to repeated substance exposure, which might be related to drug craving and relapse. The effects of amphetamine on locomotor activity and locomotor sensitization were enhanced in M (5) (-/-) mice, while the effects of cocaine were similar in M (5) (-/-) and wild-type mice. RESULTS: Consistent with the behavioral results, amphetamine-, but not cocaine, -elicited dopamine release in nucleus accumbens was enhanced in M (5) (-/-) mice. DISCUSSION: The different effects of amphetamine and cocaine in M (5) (-/-) mice may be due to the divergent pharmacological profile of the two drugs, where amphetamine, but not cocaine, is able to release intracellular stores of dopamine. In conclusion, we show here for the first time that amphetamine-induced hyperactivity and dopamine release as well as amphetamine sensitization are enhanced in mice lacking the M(5) receptor. These results support the concept that the M(5) receptor modulates effects of addictive drugs.

AB - INTRODUCTION: Muscarinic M(5) receptors are the only muscarinic receptor subtype expressed by dopamine-containing neurons of the ventral tegmental area. These cells play an important role for the reinforcing properties of psychostimulants and M(5) receptors modulate their activity. Previous studies showed that M(5) receptor knockout (M (5) (-/-) ) mice are less sensitive to the reinforcing properties of addictive drugs. MATERIALS AND METHODS: Here, we investigate the role of M(5) receptors in the effects of amphetamine and cocaine on locomotor activity, locomotor sensitization, and dopamine release using M (5) (-/-) mice backcrossed to the C57BL/6NTac strain. STATISTICAL ANALYSES: Sensitization of the locomotor response is considered a model for chronic adaptations to repeated substance exposure, which might be related to drug craving and relapse. The effects of amphetamine on locomotor activity and locomotor sensitization were enhanced in M (5) (-/-) mice, while the effects of cocaine were similar in M (5) (-/-) and wild-type mice. RESULTS: Consistent with the behavioral results, amphetamine-, but not cocaine, -elicited dopamine release in nucleus accumbens was enhanced in M (5) (-/-) mice. DISCUSSION: The different effects of amphetamine and cocaine in M (5) (-/-) mice may be due to the divergent pharmacological profile of the two drugs, where amphetamine, but not cocaine, is able to release intracellular stores of dopamine. In conclusion, we show here for the first time that amphetamine-induced hyperactivity and dopamine release as well as amphetamine sensitization are enhanced in mice lacking the M(5) receptor. These results support the concept that the M(5) receptor modulates effects of addictive drugs.

U2 - 10.1007/s00213-009-1685-2

DO - 10.1007/s00213-009-1685-2

M3 - Journal article

VL - 207

SP - 547

EP - 558

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 4

ER -

ID: 170944