Abstract
Concomitant use of anabolic androgenic steroids and cocaine has increased in the last years. However, the effects of chronic exposure to these substances during adolescence on cardiovascular function are unknown. Here, we investigated the effects of treatment for 10 consecutive days with testosterone and cocaine alone or in combination on basal cardiovascular parameters, baroreflex activity, hemodynamic responses to vasoactive agents, and cardiac morphology in adolescent rats. Administration of testosterone alone increased arterial pressure, reduced heart rate (HR), and exacerbated the tachycardiac baroreflex response. Cocaine-treated animals showed resting bradycardia without changes in arterial pressure and baroreflex activity. Combined treatment with testosterone and cocaine did not affect baseline arterial pressure and HR, but reduced baroreflex-mediated tachycardia. None of the treatments affected arterial pressure response to either vasoconstrictor or vasodilator agents. Also, heart to body ratio and left and right ventricular wall thickness were not modified by drug treatments. However, histological analysis of left ventricular sections of animals subjected to treatment with testosterone and cocaine alone and combined showed a greater spacing between cardiac muscle fibers, dilated blood vessels, and fibrosis. These data show important cardiovascular changes following treatment with testosterone in adolescent rats. However, the results suggest that exposure to cocaine alone or combined with testosterone during adolescence minimally affect cardiovascular function.
Highlights
Adolescence is a critical period of vulnerability for development of drug addiction [1]
Several pieces of evidence suggest a greater vulnerability of adolescents to the behavioral and neurochemical consequences of cocaine and anabolic steroids (AAS) exposure [29,30,31,32,33]
In the present study we report that: (i) treatment for 10 days with testosterone alone increased basal values of arterial pressure, but this effect was abolished when cocaine was coadministrated; (ii) treatment with either testosterone or cocaine alone evoked resting bradycardia, but combined treatment with these substances did not affect heart rate (HR); (iii) treatment with testosterone alone increased reflex tachycardia to blood pressure decreases and reduced maximum reflex bradycardia to increase in blood pressure, while cocaine reduced both maximum reflex bradycardia and tachycardia
Summary
Adolescence is a critical period of vulnerability for development of drug addiction [1]. Epidemiological studies indicate that earlier onset of substance use predicts greater likelihood of development of substance use disorders [4,5,6]. These latter findings are associated with clinical and preclinical results demonstrating that adolescents are undergoing developmental changes in primary motivational circuitry, which can influence the amount of drug intake, psychopharmacological responsivity and the susceptibility to development of drug dependence [1,7]. Emerging data indicate that AAS use among adolescents is frequently associated with abuse of other substances, and cocaine is the drug most frequently coabused with AAS [8,9]. These pieces of evidence are alarming because numerous clinical and experimental reports document the adverse effects of cocaine and AAS abuse in adulthood, a limited number of studies have assessed the potential toxic effects of the abuse of these substances, specially their concomitant use, in adolescents
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