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Therapeutic-like properties of a dopamine uptake inhibitor in animal models of amphetamine addiction.
Int J Neuropsychopharmacol. 2011 Jun; 14(5):655-65.IJ

Abstract

N-substituted benztropine (BZT) analogs are molecules that display high affinity for the dopamine transporter (DAT), therapeutic-like effects in animal models of cocaine abuse, and psychopharmacological characteristics consistent with those of a substitute medication for cocaine addiction. Since amphetamine (Amph) and cocaine share mechanisms of action at the DAT, we evaluated the effectiveness of a BZT analog in animal models of Amph addiction. We tested in mice and rats the effects of the BZT derivative, 3α-[bis(4-fluorophenyl)methoxy]-tropane (AHN-1055), on Amph-induced conditioned place preference (CPP), locomotor activity, sensitization, self-administration and ΔFosB accumulation in the nucleus accumbens (NAc). The results showed that AHN-1055 did not produce rewarding, stimulant, or sensitized locomotor effects in mice when administered alone but it readily blocked the rewarding, stimulant, and sensitizing effects of repeated Amph exposure. Furthermore, in mice undergoing conditioning in the CPP paradigm, the BZT analog prevented the accumulation of ΔFosB protein induced in the NAc shell region by Amph treatment. Notably, treatment with AHN-1055 dose-dependently reduced Amph self-administration in rats with a steady history of voluntary Amph intake. These results provide a straightforward demonstration that a BZT derivative with binding affinity for DAT exhibits high efficacy in animal models of Amph abuse, suggesting that the novel generation of BZT analogs could have wider therapeutic applications in stimulant-spectrum disorders than those previously recognized.

Authors+Show Affiliations

Biopsychology & Comparative Neuroscience, Cavanilles Institute (ICBiBE), University of Valencia-FGUV, Valencia, Spain.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20735880

Citation

Velazquez-Sanchez, Clara, et al. "Therapeutic-like Properties of a Dopamine Uptake Inhibitor in Animal Models of Amphetamine Addiction." The International Journal of Neuropsychopharmacology, vol. 14, no. 5, 2011, pp. 655-65.
Velazquez-Sanchez C, Ferragud A, Renau-Piqueras J, et al. Therapeutic-like properties of a dopamine uptake inhibitor in animal models of amphetamine addiction. Int J Neuropsychopharmacol. 2011;14(5):655-65.
Velazquez-Sanchez, C., Ferragud, A., Renau-Piqueras, J., & Canales, J. J. (2011). Therapeutic-like properties of a dopamine uptake inhibitor in animal models of amphetamine addiction. The International Journal of Neuropsychopharmacology, 14(5), 655-65. https://doi.org/10.1017/S1461145710000969
Velazquez-Sanchez C, et al. Therapeutic-like Properties of a Dopamine Uptake Inhibitor in Animal Models of Amphetamine Addiction. Int J Neuropsychopharmacol. 2011;14(5):655-65. PubMed PMID: 20735880.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapeutic-like properties of a dopamine uptake inhibitor in animal models of amphetamine addiction. AU - Velazquez-Sanchez,Clara, AU - Ferragud,Antonio, AU - Renau-Piqueras,Jaime, AU - Canales,Juan J, Y1 - 2010/08/24/ PY - 2010/8/26/entrez PY - 2010/8/26/pubmed PY - 2012/1/10/medline SP - 655 EP - 65 JF - The international journal of neuropsychopharmacology JO - Int. J. Neuropsychopharmacol. VL - 14 IS - 5 N2 - N-substituted benztropine (BZT) analogs are molecules that display high affinity for the dopamine transporter (DAT), therapeutic-like effects in animal models of cocaine abuse, and psychopharmacological characteristics consistent with those of a substitute medication for cocaine addiction. Since amphetamine (Amph) and cocaine share mechanisms of action at the DAT, we evaluated the effectiveness of a BZT analog in animal models of Amph addiction. We tested in mice and rats the effects of the BZT derivative, 3α-[bis(4-fluorophenyl)methoxy]-tropane (AHN-1055), on Amph-induced conditioned place preference (CPP), locomotor activity, sensitization, self-administration and ΔFosB accumulation in the nucleus accumbens (NAc). The results showed that AHN-1055 did not produce rewarding, stimulant, or sensitized locomotor effects in mice when administered alone but it readily blocked the rewarding, stimulant, and sensitizing effects of repeated Amph exposure. Furthermore, in mice undergoing conditioning in the CPP paradigm, the BZT analog prevented the accumulation of ΔFosB protein induced in the NAc shell region by Amph treatment. Notably, treatment with AHN-1055 dose-dependently reduced Amph self-administration in rats with a steady history of voluntary Amph intake. These results provide a straightforward demonstration that a BZT derivative with binding affinity for DAT exhibits high efficacy in animal models of Amph abuse, suggesting that the novel generation of BZT analogs could have wider therapeutic applications in stimulant-spectrum disorders than those previously recognized. SN - 1469-5111 UR - https://www.unboundmedicine.com/medline/citation/20735880/Therapeutic_like_properties_of_a_dopamine_uptake_inhibitor_in_animal_models_of_amphetamine_addiction_ L2 - https://academic.oup.com/ijnp/article-lookup/doi/10.1017/S1461145710000969 DB - PRIME DP - Unbound Medicine ER -