Cerebrospinal fluid and behavioral changes after methyltestosterone administration - Preliminary findings
ABSTRACT Anabolic androgen steroid abuse is associated with multiple psychiatric symptoms and is a significant public health problem. The biological mechanisms underlying behavioral symptom development are poorly understood.
We examined levels of monoamine metabolites, neurohormones, and neuropeptides in the cerebrospinal fluid (CSF) of 17 healthy men, at baseline and following 6 days of methyltestosterone (MT) administration (3 days of 40 mg/d, then 3 days of 240 mg/d). Subjects received MT or placebo in a fixed sequence, with neither subjects nor raters aware of the order. Potential relationships were examined between CSF measures, CSF MT levels, and behavioral changes measured on a visual analog scale.
Following MT administration, levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were significantly lower (mean +/- SD, 103.8 +/- 47 vs 122.0 +/- 50.7 pmol/mL; P<.01), and 5-hydroxyindoleacetic acid (5-HIAA) levels were significantly higher (mean +/- SD, 104.7 +/- 31.3 vs 86.9 +/- 23.6 pmol/mL; P<.01). No significant MT-related changes were observed in CSF levels of corticotropin, norepinephrine, cortisol, arginine vasopressin, prolactin, corticotropin-releasing hormone, beta-endorphin, and somatotropin release-inhibiting factor. Changes in CSF 5-HIAA significantly correlated with increases in "activation" symptoms (energy, sexual arousal, and diminished sleep) (r = 0.55; P =.02). No significant correlation was observed between changes in CSF and plasma MT, CSF MHPG, and behavioral symptoms.
Short-term anabolic androgenic steroid use affects brain neurochemistry, increasing CSF 5-HIAA and decreasing MHPG. Changes in 5-HIAA levels caused by anabolic androgenic steroids are related to the behavioral changes we observed. In this small sample, we did not observe a significant relationship between behavioral measures and either dose of MT or CSF and plasma levels of MT.
SourceAvailable from: Henk Barendregt[Show abstract] [Hide abstract]
ABSTRACT: Beta-endorphin (β-END) is an opioid neuropeptide which has an important role in the development of hypotheses concerning the non-synaptic or paracrine communication of brain messages. This kind of communication between neurons has been designated volume transmission (VT) to differentiate it clearly from synaptic communication. VT occurs over short as well as long distances via the extracellular space in the brain, as well as via the cerebrospinal fluid (CSF) flowing through the ventricular spaces inside the brain and the arachnoid space surrounding the central nervous system (CNS). To understand how β-END can have specific behavioral effects, we use the notion behavioral state, inspired by the concept of machine state, coming from Turing (Proc London Math Soc, Series 2,42:230-265, 1937). In section 1.4 the sequential organization of male rat behavior is explained showing that an animal is not free to switch into another state at any given moment. Funneling-constraints restrict the number of possible behavioral transitions in specific phases while at other moments in the sequence the transition to other behavioral states is almost completely open. The effects of β-END on behaviors like food intake and sexual behavior, and the mechanisms involved in reward, meditation and pain control are discussed in detail. The effects on the sequential organization of behavior and on state transitions dominate the description of these effects.01/2015; 12(1):3. DOI:10.1186/2045-8118-12-3
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ABSTRACT: Anabolic-androgenic steroids (AAS) increase libido and sexual behavior, but the underlying behavioral mechanisms are unclear. One way AAS may enhance expression of sexual behavior is by increasing the willingness to work for sex. In the present study, sexually-experienced male rats received daily injections of testosterone at supraphysiologic doses (7.5mg/kg in water with 13% cyclodextrin) or vehicle and were tested for appetitive sexual behavior measured by operant responding for access to an estrous female. Initially, rats were trained in their home cage to respond on a nose-poke under a 10-min fixed-interval schedule for food reward. Once rats achieved stable response rates, the food was replaced by a female, followed by mating for 10min. There was no effect of testosterone on operant responding for food (28.1±4.4 responses/10min for testosterone, 30.6±4.3 for vehicle) or sex (35.0±4.0 responses/10min for testosterone, 37.3±5.2 for vehicle). However, rats made significantly more responses for sex than for food (p<0.05), and responses for food and sex were positively correlated among individuals (R(2)=0.6). Additional groups of rats were trained to respond on a lever for the female under a 2nd-order schedule of reinforcement, where 5 responses opened a door to show the female for 5seconds. After 15 door openings, the male gained access to the female. There was no effect of testosterone on time to complete 75 responses: 38.4±7.8minutes for vehicle controls vs 43.3±6.6minutes for testosterone-treated rats (p>0.05). These findings suggest that chronic high-dose testosterone does not enhance appetitive drive for sexual behavior.Hormones and Behavior 09/2014; 66(4). DOI:10.1016/j.yhbeh.2014.08.009 · 4.51 Impact Factor
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ABSTRACT: Background Anabolic-androgenic steroids (AASs) are abused primarily in the context of intense exercise and for the purposes of increasing muscle mass as opposed to drug-induced euphoria. AASs also modulate the HPA axis and may increase the reinforcing value of exercise through changes to stress hormone and endorphin release. To test this hypothesis, 26 adult males drawn from a larger study on AAS use completed a progressive ratio task designed to examine the reinforcing value of exercise relative to financial reinforcer. Method Sixteen experienced and current users (8 on-cycle, 8 off-cycle) and 10 controls matched on quantity x frequency of exercise, age, and education abstained from exercise for 24 hours prior to testing and provided 24-hour cortisol, plasma cortisol, ACTH, β-endorphin samples, and measures of mood, compulsive exercise, and body image. Results Between group differences indicated that on-cycle AAS users had the highest β-endorphin levels, lowest cortisol levels, higher ACTH levels than controls. Conversely, off-cycle AAS users had the highest cortisol and ACTH levels, but the lowest β-endorphin levels. Exercise value was positively correlated with β-endorphin and symptoms of AAS dependence. Conclusion The HPA response to AASs may explain why AASs are reinforcing in humans and exercise may play a key role in the development of AAS dependence.Drug and Alcohol Dependence 06/2014; DOI:10.1016/j.drugalcdep.2014.03.008 · 3.28 Impact Factor
Dennis L Murphy