Neuropeptide Y Y5 receptor antagonism attenuates cocaine-induced effects in mice.
Research output: Contribution to journal › Journal article › peer-review
Standard
Neuropeptide Y Y5 receptor antagonism attenuates cocaine-induced effects in mice. / Sørensen, Gunnar; Jensen, Morten; Weikop, Pia; Nielsen, Ditte Dencker; Christiansen, Søren Hofman Oliveira; Løland, Claus Juul; Bengtsen, Cecilie Hee; Petersen, Jørgen Holm; Fink-Jensen, Anders; Wörtwein, Gitta; Woldbye, David Paul Drucker.
In: Psychopharmacology, Vol. 222, 02.2012, p. 565-577.Research output: Contribution to journal › Journal article › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Neuropeptide Y Y5 receptor antagonism attenuates cocaine-induced effects in mice.
AU - Sørensen, Gunnar
AU - Jensen, Morten
AU - Weikop, Pia
AU - Nielsen, Ditte Dencker
AU - Christiansen, Søren Hofman Oliveira
AU - Løland, Claus Juul
AU - Bengtsen, Cecilie Hee
AU - Petersen, Jørgen Holm
AU - Fink-Jensen, Anders
AU - Wörtwein, Gitta
AU - Woldbye, David Paul Drucker
PY - 2012/2
Y1 - 2012/2
N2 - Rationale Several studies suggest a role for neuropeptide Y (NPY) in addiction to drugs of abuse, including cocaine. However, the NPY receptors mediating addiction-related effects remain to be determined. Objectives To explore the potential role of Y5 NPY receptors in cocaine-induced behavioural effects. Methods The Y5 antagonist L-152,804 and Y5-knockout (Y5-KO) mice were tested in two models of cocaine addiction-related behaviour: acute self-administration and cocaine-induced hyperactivity. We also studied effects of Y5 receptor antagonism on cocaine-induced c-fos expression and extracellular dopamine with microdialysis as well as dopamine transporter-mediated uptake of dopamine in vitro. Immunocytochemistry was used to determine whether dopamine neurons express Y5-like immunoreactivity. Results In self-administration, L-152,804 prominently decreased nose-poking for the peak dose of cocaine and shifted the dose–response curve for cocaine downward. Y5-KO mice also showed modestly attenuated selfadministration. Cocaine-induced hyperactivity was attenuated by L-152,804 and in Y5-KO mice. Cocaine failed to increase c-fos expression in the nucleus accumbens and striatum of L-152,804-treated mice, indicating that the Y5 antagonist could act by influencing neural activity in these regions. Accordingly, the cocaine-induced increase in accumbal extracellular dopamine was attenuated by L- 152,804 and in Y5-KO mice, suggesting that Y5 antagonism influences cocaine-induced behaviour by regulating dopamine. Consistent with this concept, dopamine neurons in the ventral tegmental area appeared to contain Y5 receptors. In contrast, neither L-152,804 nor NPY influenced dopamine transporter-mediated dopamine uptake. Conclusions The present data indicate that Y5 antagonism may attenuate cocaine-induced behavioural effects, suggesting that Y5 receptors could be a potential therapeutic target in cocaine addiction.
AB - Rationale Several studies suggest a role for neuropeptide Y (NPY) in addiction to drugs of abuse, including cocaine. However, the NPY receptors mediating addiction-related effects remain to be determined. Objectives To explore the potential role of Y5 NPY receptors in cocaine-induced behavioural effects. Methods The Y5 antagonist L-152,804 and Y5-knockout (Y5-KO) mice were tested in two models of cocaine addiction-related behaviour: acute self-administration and cocaine-induced hyperactivity. We also studied effects of Y5 receptor antagonism on cocaine-induced c-fos expression and extracellular dopamine with microdialysis as well as dopamine transporter-mediated uptake of dopamine in vitro. Immunocytochemistry was used to determine whether dopamine neurons express Y5-like immunoreactivity. Results In self-administration, L-152,804 prominently decreased nose-poking for the peak dose of cocaine and shifted the dose–response curve for cocaine downward. Y5-KO mice also showed modestly attenuated selfadministration. Cocaine-induced hyperactivity was attenuated by L-152,804 and in Y5-KO mice. Cocaine failed to increase c-fos expression in the nucleus accumbens and striatum of L-152,804-treated mice, indicating that the Y5 antagonist could act by influencing neural activity in these regions. Accordingly, the cocaine-induced increase in accumbal extracellular dopamine was attenuated by L- 152,804 and in Y5-KO mice, suggesting that Y5 antagonism influences cocaine-induced behaviour by regulating dopamine. Consistent with this concept, dopamine neurons in the ventral tegmental area appeared to contain Y5 receptors. In contrast, neither L-152,804 nor NPY influenced dopamine transporter-mediated dopamine uptake. Conclusions The present data indicate that Y5 antagonism may attenuate cocaine-induced behavioural effects, suggesting that Y5 receptors could be a potential therapeutic target in cocaine addiction.
U2 - 10.1007/s00213-012-2651-y
DO - 10.1007/s00213-012-2651-y
M3 - Journal article
C2 - 22367168
VL - 222
SP - 565
EP - 577
JO - Psychopharmacology
JF - Psychopharmacology
SN - 0033-3158
ER -
ID: 38468992