Cardiovascular effects of chronic administration of cocaine and testosterone in rats

• Grant number: 10/16192-8
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2011
• End date: December 31, 2012
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Carlos Cesar Crestani
• Grantee: Carlos Cesar Crestani
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Several studies have shown an increase in use of cocaine and anabolic-androgenic steroids (AAS). Moreover, use of AAS is associated with consumption of cocaine. There are some evidences in the literature suggesting that use of AAS and cocaine is associated with a variety of cardiovascular diseases, including: hypertension and cardiac diseases. Although relevance of this issue, mechanisms involved in cardiovascular diseases associated with chronic use of AAS and cocaine, especially simultaneous consumption of these drugs, are still poorly understood.There are no reports in the literature of the effects of chronic treatment with cocaine, testosterone or simultaneous administration of these drugs in the baroreflex activity. Studies have suggested that decreased baroreflex activity is an important mechanism involved in hypertension, and is a risk factor for the development of cardiac arrhythmia and sudden death in several cardiovascular diseases. Although some in vitro studies to report impaired vascular responses to vasoactive substances after chronic administration of cocaine or AAS, there are no in vivo studies reporting effect of chronic administration of these drugs in vascular reactivity. An impaired vascular response is a precursor and a marker of atherosclerotic disease and changes in the action of vasodilator and vasoconstrictor agents, and has been proposed as a mechanism involved in development of hypertension. Some studies have suggested that chronic use of cocaine change stress-evoked cardiovascular and neuroendocrine responses. However, effect of administration of testosterone or simultaneous administration of testosterone and cocaine in autonomic and neuroendocrine responses to stress has never been reported. Finally, it has been demonstrated that chronic administration of cocaine or testosterone evokes functional changes in central nervous system (CNS) structures involved in cardiovascular control. Some studies have suggested that the bed nucleus of the stria terminalis (BST) is one of the main regions in the CNS to show changes after cocaine chronic exposure. Thus, the present study will test the hypothesis that repeated administration of testosterone and/or cocaine evokes changes on arterial pressure (AP) and heart rate (HR) baseline, baroreflex activity, vascular reactivity and stress-evoked autonomic and neuroendocrine responses in rats. Moreover, we will investigate if cardiovascular changes resulting from chronic treatment with these drugs are associated with alterations in control of baroreflex activity and stress-evoked autonomic and neuroendocrine responses by the bed nucleus of the stria terminalis. For this, we will investigate the effect of repeated administration of testosterone and/or cocaine in the basal values of mean, systolic, diastolic AP and HR; baroreflex activity; vascular reactivity to vasodilator and vasoconstrictor agents and autonomic and neuroendocrine responses to acute restraint stress. We will also study the effect of these treatments in control of baroreflex activity and restraint stress-evoked autonomic and neuroendocrine responses by BNST of rats. (AU)

Scientific publications

(10)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GOMES, FELIPE V.; ALVES, FERNANDO H. F.; GUIMARAES, FRANCISCO S.; CORREA, FERNANDO M. A.; RESSTEL, LEONARDO B. M.; CRESTANI, CARLOS C.. Cannabidiol administration into the bed nucleus of the stria terminalis alters cardiovascular responses induced by acute restraint stress through 5-HT1A receptor. European Neuropsychopharmacology, v. 23, n. 9, p. 1096-1104, SEP 2013. (11/07332-3, 07/03685-3, 10/16192-8)

CRUZ, FABIO C.; ENGI, SHEILA A.; LEAO, RODRIGO M.; PLANETA, CLEOPATRA S.; CRESTANI, CARLOS C.. Influence of the single or combined administration of cocaine and testosterone in autonomic and neuroendocrine responses to acute restraint stress. JOURNAL OF PSYCHOPHARMACOLOGY, v. 26, n. 10, p. 1366-1374, OCT 2012. (10/16192-8)

CRESTANI, CARLOS C.; ALVES, FERNANDO H. F.; GOMES, FELIPE V.; RESSTEL, LEONARDO B. M.; CORREA, FERNANDO M. A.; HERMAN, JAMES P.. Mechanisms in the Bed Nucleus of the Stria Terminalis Involved in Control of Autonomic and Neuroendocrine Functions: A Review. Current Neuropharmacology, v. 11, n. 2, p. 141-159, MAR 2013. (10/16192-8)

CRESTANI, CARLOS C.; TAVARES, RODRIGO F.; GUIMARAES, FRANSCISCO S.; CORREA, FERNANDO M. A.; JOCA, SAMIA R. L.; RESSTEL, LEONARDO B. M.. Chronic fluoxetine treatment alters cardiovascular functions in unanesthetized rats. European Journal of Pharmacology, v. 670, n. 2-3, p. 527-533, NOV 30 2011. (11/07332-3, 10/16192-8)

ENGI, SHEILA A.; CRUZ, FABIO C.; LEAO, RODRIGO M.; CORREA, FERNANDO M.; PLANETA, CLEOPATRA S.; CRESTANI, CARLOS C.. Effect of the Single or Combined Administration of Cocaine and Testosterone on Cardiovascular Function and Baroreflex Activity in Unanesthetized Rats. Journal of Cardiovascular Pharmacology, v. 59, n. 3, p. 231-240, MAR 2012. (10/16192-8)

CAMARGO, LAURA H. A.; ALVES, FERNANDO H. F.; BIOJONE, CAROLINE; CORREA, FERNANDO M. A.; RESSTEL, LEONARDO B. M.; CRESTANI, CARLOS C.. Involvement of N-methyl-D-aspartate glutamate receptor and nitric oxide in cardiovascular responses to dynamic exercise in rats. European Journal of Pharmacology, v. 713, n. 1-3, p. 16-24, AUG 5 2013. (11/13299-9, 10/16192-8)

CRUZ, F. C.; ALVES, F. H. F.; LEAO, R. M.; PLANETA, C. S.; CRESTANI, C. C.. ROLE OF THE BED NUCLEUS OF THE STRIA TERMINALIS IN CARDIOVASCULAR CHANGES FOLLOWING CHRONIC TREATMENT WITH COCAINE AND TESTOSTERONE: A ROLE BEYOND DRUG SEEKING IN ADDICTION?. Neuroscience, v. 253, p. 29-39, DEC 3 2013. (10/16192-8)

ENGI, SHEILA A.; CRUZ, FABIO C.; LEAO, RODRIGO M.; SPOLIDORIO, LUIS C.; PLANETA, CLEOPATRA S.; CRESTANI, CARLOS C.. Cardiovascular Complications following Chronic Treatment with Cocaine and Testosterone in Adolescent Rats. PLoS One, v. 9, n. 8, AUG 14 2014. (12/14376-0, 10/16192-8)

BUSNARDO, CRISTIANE; ALVES, FERNANDO H. F.; CRESTANI, CARLOS C.; SCOPINHO, AMERICA A.; RESSTEL, LEONARDO B. M.; CORREA, FERNANDO M. A.. Paraventricular nucleus of the hypothalamus glutamate neurotransmission modulates autonomic, neuroendocrine and behavioral responses to acute restraint stress in rats. European Neuropsychopharmacology, v. 23, n. 11, p. 1611-1622, NOV 2013. (09/05308-8, 10/09462-9, 10/16192-8)

SCOPINHO, AMERICA A.; ALVES, FERNANDO H. F.; RESSTEL, LEONARDO B. M.; CORREA, FERNANDO M. A.; CRESTANI, CARLOS C.. Lateral septal area alpha(1)-and alpha(2)-adrenoceptors differently modulate baroreflex activity in unanaesthetized rats. Experimental Physiology, v. 97, n. 9, p. 1018-1029, SEP 2012. (09/03187-9, 10/16192-8)