Increased CSF Volumes Are Associated with Diminished Subjective Responses to Cocaine Infusion

Abstract

We evaluated the hypothesis that ventricular and cortical CSF volume increases are associated with reductions in the magnitude of euphoric effects produced by intravenous IV cocaine infusion in cocaine dependent (CD) individuals. Eleven CD patients participating in a cocaine-infusion study and eleven control subjects underwent magnetic resonance imaging (MRI). Two CSF regions of interest (lateral ventricles and frontal cortex CSF) and two comparison regions (third ventricle and posterior cortex CSF) were measured. Self-reported ratings of the intensity of euphoric response ("high") were obtained from the CD subjects at 3, 10, and 30 minutes after IV administration of cocaine. A significant negative correlation was observed between the volume of the lateral ventricles and subjective ratings of the "high" experienced at 3 minutes, but not at 10 The relationship between brain variables and subjective effects of cocaine has not been extensively studied. Morgan et al. (1993), using non-contrast computerized tomography (CT), examined the association between ventricular brain ratio (VBR) and intensity of response to the effects of 40 mg of intravenous cocaine. They obtained subjective ratings of drug effect every minute for 30 minutes after the cocaine injection and observed a significant negative correlation (r ϭ Ϫ .53, p ϭ .02) between VBR and the average rating of drug response over the first 10 minute interval but no relationship over the last two 10 minute intervals (r ϭ Ϫ .22 and r ϭ (Morgan et al. 1993). This suggested that subjects with larger ventricles had reduced sensitivity to cocaine's immediate euphoric effects.As part of a recent study investigating the possible attenuating effects of selegiline on cocaine-induced euphoria and brain metabolism (Bartzokis et al. 1999a), non-treatment seeking "crack" cocaine smokers were evaluated with magnetic resonance imaging (MRI) of the brain in order to identify patients with enlarged ventricles who may be less responsive to IV cocaine's euphoric effects. The total volume of the lateral ventricles was measured in order to evaluate the magnitude of the negative association between this volume measure and the experience of euphoria ("high") associated with cocaine infusion. The volume of the third ventricle was also measured in order to assess whether this structure/function association was specific to the lateral ventricles or a phenomenon associated with generalized ventriculomegaly.In addition, the volume of the supracortical cerebrospinal fluid (CSF) in the frontal region of the cerebral cortex was measured in order to indirectly assess whether reduced frontal cortex gray matter observed in the polysubstance dependent (Liu et al. 1998) and alcohol dependent (Pfefferbaum et al. 1998) populations is also associated with a diminished intensity of cocaine infusion-induced euphoria. As with the ventricular volumes, we hypothesized that the volume of CSF in this cortical region will also correlate negatively to the cocaine infusion-associated experience of euphoria...

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“…These results agree with those of most previous studies that reported that global brain atrophy does not follow cocaine addiction [37-39; but see 40, 41]. …”

Prenatal cocaine effects on brain structure in early infancy

“…CSF enlargement is also consistent with adult cocaine or alcohol abuse and suggestive of response to neuronal injury. Cocaine-dependent adults exhibit increased cortical CSF volume (Bartzokis et al 2000). Alcohol-related GM and WM loss is linked to enhanced CSF volumes, which decrease proportionally with longer abstinence (Demirakca et al 2011).…”

The Subjective Effects of Cocaine: Relationship to Years of Cocaine Use and Current Age

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