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

Lene S Schmidt; Anthony D Miller; Deranda B Lester; Cecilie Bay-Richter; Christina Schülein; Henriette Frikke-Schmidt; Jürgen Wess; Charles D Blaha; David P D Woldbye; Anders Fink-Jensen; Gitta Wörtwein

doi:10.1007/s00213-009-1685-2

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

Lene S Schmidt, Anthony D Miller, Deranda B Lester, Cecilie Bay-Richter, Christina Schülein, Henriette Frikke-Schmidt, Jürgen Wess, Charles D Blaha, David P D Woldbye, Anders Fink-Jensen, Gitta Wörtwein

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

32 Citationer (Scopus)

Abstract

Udgivelsesdato: 2010-Jan

Originalsprog	Engelsk
Tidsskrift	Psychopharmacology
Vol/bind	207
Udgave nummer	4
Sider (fra-til)	547-58
Antal sider	11
ISSN	0033-3158
DOI	https://doi.org/10.1007/s00213-009-1685-2
Status	Udgivet - 2010

Bibliografisk note

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

Adgang til dokumentet

10.1007/s00213-009-1685-2

Citationsformater

Schmidt, L. S., Miller, A. D., Lester, D. B., Bay-Richter, C., Schülein, C., Frikke-Schmidt, H., Wess, J., Blaha, C. D., Woldbye, D. P. D., Fink-Jensen, A., & Wörtwein, G. (2010). 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

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 2010, 'Increased amphetamine-induced locomotor activity, sensitization, and accumbal dopamine release in M5 muscarinic receptor knockout mice', Psychopharmacology, bind 207, nr. 4, s. 547-58. https://doi.org/10.1007/s00213-009-1685-2

@article{3a44f330430c11df928f000ea68e967b,

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 = "2010",

doi = "10.1007/s00213-009-1685-2",

language = "English",

volume = "207",

pages = "547--58",

journal = "Psychopharmacology",

issn = "0033-3158",

publisher = "Springer",

number = "4",

}

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 - 2010

Y1 - 2010

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

C2 - 19820917

SN - 0033-3158

VL - 207

SP - 547

EP - 558

JO - Psychopharmacology

JF - Psychopharmacology

IS - 4

ER -