Tags

Type your tag names separated by a space and hit enter

Calcium Channel Antagonist Isradipine Attenuates Cocaine-Induced Motor Activity in Rats: Correlation with Brain Monoamine Levelsa.
Ann N Y Acad Sci. 1998 May; 844(1):201-207.AN

Abstract

Cocaine is a widely abused psychomotor stimulant which acts in the central nervous system (CNS) by blocking the reuptake site. It has been estimated that between 30-60million people have abused cocaine in the United States. Unfortunately, an effective therapy for cocaine abuse is not available. The calcium channel antagonists (CCAs) are commonly used in the therapy of various cardiovascular diseases and are under investigation due to their potential in modulating calcium-dependent neurotransmitter release. The purpose of this study was to evaluate the acute effect of isradipine on cocaine-induced locomotor and stereotypic activity and correlate the changes in dopamine, serotonin and their metabolites-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA)-levels in the rat brain. Animals were pretreated intraperitoneally (i.p.) with vehicle or CCAs. After 30 minutes they were administered cocaine (20 mg/kg, i.p.). During this period, motor and stereotypic activity was monitored. In a separate experiment, animals were dosed as described above and were sacrificed by decapitation after the 30-minute treatment period. The nucleus accumbens and caudate nucleus were dissected and analyzed for monoamines using a high-performance liquid chromatography-electrochemical detector (HPLC-ECD). Isradipine (5mg/kg, i.p.) inhibited cocaine-induced locomotor and stereotypic activity by 49% and 36%, respectively, as compared to controls. In the nucleus accumbens cocaine (20 mg/kg, i.p.) increased extracellular dopamine and serotonin levels by 28% and 73%, respectively, as compared to controls. Isradipine (5 mg/kg, i.p.) pretreatment decreased cocaine-induced extracellular dopamine levels in the nucleus accumbens by 8% while decreasing serotonin levels by 9%. Cocaine (20 mg/kg, i.p.) produced increased levels of both extracellular dopamine and serotonin (9% and 4%, respectively) in the caudate nucleus. Isradipine (5 mg/kg, i.p.) pretreatment decreased cocaine (20 mg/kg i.p.)-induced extracellular dopamine and serotonin levels in the caudate nucleus by 18% and 8%, respectively. These experiments suggest that a central mechanism may be involved in attenuation of cocaine-induced motor behaviors by isradipine.

Authors+Show Affiliations

Department of Pharmacology, Meharry Medical College, 1005 DB Todd Boulevard, Nashville, Tennessee 37208, USANeurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/FDA, 3900 NCTR Drive, Jefferson, Arkansas 72079-9502, USA.Department of Pharmacology, Meharry Medical College, 1005 DB Todd Boulevard, Nashville, Tennessee 37208, USANeurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/FDA, 3900 NCTR Drive, Jefferson, Arkansas 72079-9502, USA.Department of Pharmacology, Meharry Medical College, 1005 DB Todd Boulevard, Nashville, Tennessee 37208, USANeurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/FDA, 3900 NCTR Drive, Jefferson, Arkansas 72079-9502, USA.Department of Pharmacology, Meharry Medical College, 1005 DB Todd Boulevard, Nashville, Tennessee 37208, USANeurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/FDA, 3900 NCTR Drive, Jefferson, Arkansas 72079-9502, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29090812

Citation

Mills, K, et al. "Calcium Channel Antagonist Isradipine Attenuates Cocaine-Induced Motor Activity in Rats: Correlation With Brain Monoamine Levelsa." Annals of the New York Academy of Sciences, vol. 844, no. 1, 1998, pp. 201-207.
Mills K, Ansah TA, Ali SF, et al. Calcium Channel Antagonist Isradipine Attenuates Cocaine-Induced Motor Activity in Rats: Correlation with Brain Monoamine Levelsa. Ann N Y Acad Sci. 1998;844(1):201-207.
Mills, K., Ansah, T. A., Ali, S. F., & Shockley, D. C. (1998). Calcium Channel Antagonist Isradipine Attenuates Cocaine-Induced Motor Activity in Rats: Correlation with Brain Monoamine Levelsa. Annals of the New York Academy of Sciences, 844(1), 201-207. https://doi.org/10.1111/j.1749-6632.1998.tb08235.x
Mills K, et al. Calcium Channel Antagonist Isradipine Attenuates Cocaine-Induced Motor Activity in Rats: Correlation With Brain Monoamine Levelsa. Ann N Y Acad Sci. 1998;844(1):201-207. PubMed PMID: 29090812.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Calcium Channel Antagonist Isradipine Attenuates Cocaine-Induced Motor Activity in Rats: Correlation with Brain Monoamine Levelsa. AU - Mills,K, AU - Ansah,T A, AU - Ali,S F, AU - Shockley,D C, PY - 2017/11/2/entrez PY - 1998/5/1/pubmed PY - 1998/5/1/medline SP - 201 EP - 207 JF - Annals of the New York Academy of Sciences JO - Ann. N. Y. Acad. Sci. VL - 844 IS - 1 N2 - Cocaine is a widely abused psychomotor stimulant which acts in the central nervous system (CNS) by blocking the reuptake site. It has been estimated that between 30-60million people have abused cocaine in the United States. Unfortunately, an effective therapy for cocaine abuse is not available. The calcium channel antagonists (CCAs) are commonly used in the therapy of various cardiovascular diseases and are under investigation due to their potential in modulating calcium-dependent neurotransmitter release. The purpose of this study was to evaluate the acute effect of isradipine on cocaine-induced locomotor and stereotypic activity and correlate the changes in dopamine, serotonin and their metabolites-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA)-levels in the rat brain. Animals were pretreated intraperitoneally (i.p.) with vehicle or CCAs. After 30 minutes they were administered cocaine (20 mg/kg, i.p.). During this period, motor and stereotypic activity was monitored. In a separate experiment, animals were dosed as described above and were sacrificed by decapitation after the 30-minute treatment period. The nucleus accumbens and caudate nucleus were dissected and analyzed for monoamines using a high-performance liquid chromatography-electrochemical detector (HPLC-ECD). Isradipine (5mg/kg, i.p.) inhibited cocaine-induced locomotor and stereotypic activity by 49% and 36%, respectively, as compared to controls. In the nucleus accumbens cocaine (20 mg/kg, i.p.) increased extracellular dopamine and serotonin levels by 28% and 73%, respectively, as compared to controls. Isradipine (5 mg/kg, i.p.) pretreatment decreased cocaine-induced extracellular dopamine levels in the nucleus accumbens by 8% while decreasing serotonin levels by 9%. Cocaine (20 mg/kg, i.p.) produced increased levels of both extracellular dopamine and serotonin (9% and 4%, respectively) in the caudate nucleus. Isradipine (5 mg/kg, i.p.) pretreatment decreased cocaine (20 mg/kg i.p.)-induced extracellular dopamine and serotonin levels in the caudate nucleus by 18% and 8%, respectively. These experiments suggest that a central mechanism may be involved in attenuation of cocaine-induced motor behaviors by isradipine. SN - 1749-6632 UR - https://www.unboundmedicine.com/medline/citation/29090812/Calcium_Channel_Antagonist_Isradipine_Attenuates_Cocaine_Induced_Motor_Activity_in_Rats:_Correlation_with_Brain_Monoamine_Levelsa_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0077-8923&date=1998&volume=844&spage=201 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.