Drug and Alcohol Dependence 62 (2001) 49–56 Quantitative medial temporal lobe brain morphology and hypothalamic-pituitary-adrenal axis function in cocaine dependence: a preliminary report Leslie K. Jacobsen a, *, Jay N. Giedd b , Mary Jeanne Kreek c , Christopher Gottschalk a , Thomas R. Kosten a a Department of Psychiatry, Yale Uniersity School of Medicine and the VA Connecticut Healthcare System, 950 Campbell Aenue, West Haen, CT 06516, USA b Child Psychiatry Branch, NIMH, Bethesda, MD20892, USA c Laboratory on the Biology of Addictie Diseases, Rockefeller Uniersity, New York, NY10021, USA Received 31 March 2000; received in revised form 23 May 2000; accepted 23 May 2000 Abstract Preclinical and clinical studies have shown that cocaine increases plasma adrenocorticotropin hormone (ACTH) and cortisol. Chronic elevation of plasma cortisol exerts direct toxic effects upon hippocampal neurons and exacerbates hippocampal damage resulting from ischemia and seizures. The authors tested for evidence of hippocampal damage in patients with chronic cocaine dependence. Medial temporal lobe and total brain volumes were quantified using magnetic resonance imaging (MRI) in 27 patients with cocaine dependence and 16 healthy subjects. Basal and ovine corticotropin releasing hormone (oCRH) stimulated ACTH and cortisol levels were also examined in a subset of 8 healthy and 9 cocaine dependent subjects after 21 days of abstinence. No evidence for decreased hippocampal or total brain volume in cocaine dependence was observed. Similarly, basal and oCRH stimulated ACTH and cortisol levels in cocaine dependent patients did not differ from those in healthy subjects. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Brain imaging; Hormonal effects; Magnetic resonance imaging; Cocaine dependence www.elsevier.com/locate/drugalcdep 1. Introduction Several lines of evidence have implicated hypothala- mic-pituitary-adrenal (HPA) axis hormones in the ini- tiation and maintenance of psychostimulant self administration. Preclinical work has shown that rats exhibiting a more sustained corticosterone response to novelty stress are significantly more prone to acquire and maintain psychostimulant self administration (Pi- azza et al., 1991). Stress has been found to increase proclivity toward at least low dose psychostimulant self administration in drug naive animals (Piazza et al., 1990; Maccari et al., 1991; Goeders and Guerin, 1994), and to induce relapse to cocaine administration in animals trained to self administer cocaine and then subjected to prolonged drug free periods (Erb et al., 1996). In humans, acute administration of cocaine increases plasma ACTH and cortisol levels (Mendelson et al., 1992; Baumann et al., 1995; Heesch et al., 1995; Mello and Mendelson, 1997; Scholar et al., 1998), with in- creases in ACTH being closely correlated with increases in plasma cocaine levels (Scholar et al., 1998). Preclini- cal work suggests that this effect of cocaine administra- tion upon ACTH and cortisol levels persists but becomes attenuated with chronic self-administration (Zhou et al., 1996). One clinical study examining this issue also found evidence for attenuation of cocaine’s effect upon ACTH and cortisol levels with chronic use, but was confounded by the presence of comorbid opi- ate dependence in the cocaine dependent subjects (Mendelson et al., 1998). * Corresponding author. Present address: National Drug and Alco- hol Research Centre, University of New South Wales, NSW 2052, Australia. Tel.: +1-203-9325711; fax: +1-203-9373886. E-mail address: leslie.jacobsen@yale.edu (L.K. Jacobsen). 0376-8716/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII:S0376-8716(00)00159-9