Monoamine and motor responses to cocaine are co-deficient in the Fawn-Hooded depressed animal model.

The Fawn-Hooded (FH) genetic animal model of depression continues to be of interest because the FH model has limited biochemical and immune function. The FH animal has an inherited trait, platelet storage pool deficiency (PSPD), an hemorrhagic disorder that is also a component of Chediak-Higashi syndrome (CHS). CHS is a pyrogenic infectious childhood disease; few patients live past the age of 20. Our hypothesis was that FH animals may exhibit different monoamine and motor responses to cocaine versus the Sprague-Dawley (SD) "normal" animal strain, which does not have the FH trait. Therefore, selective neuromolecular imaging (NMI) of the monoamines, dopamine (DA) and 5-HT within nucleus accumbens (NAcc) of behaving male FH versus SD rats was performed in vivo with BRODERICK PROBE sensors and a semiderivative voltammetric circuit. Each animal was placed in a faraday chamber and electrochemical signals were detected via a mercury commutator and flexible cable. Baseline values for neurotransmitters and behavior were derived during the last half-hour of habituation behavior. Release of DA and 5-HT was detected selectively, at separate oxidation potentials, within seconds, before and after intraperitoneal administration of the psychostimulant, cocaine (10 mg/kg). At the same time, frequencies of ambulations and central ambulations were separately monitored with infrared photobeams, which surrounded the faraday chamber. Data were compared by ANOVA analysis followed by Tukey's post hoc test. The data showed that (1) DA release in NAcc of behaving FH animals did not respond to cocaine; neither first hour nor second hour values significantly differed from baseline (both hours, p>0.05), whereas SD animals exhibited a significant increase in cocaine-induced DA release in NAcc (both hours, p<0.001). The ability for acute cocaine to increase DA release in NAcc was significantly greater in SD than in FH animals (p<0.001). (2) 5-HT release in NAcc of behaving FH animals was not significantly increased by cocaine (both hours, p>0.05), whereas 5-HT release in NAcc of SD animals was significantly increased after cocaine (both hours, p<0.001). The ability for acute cocaine to increase 5-HT release was significantly greater in SD than in FH animals (p<0.001). (3) Ambulations in the FH strain were modestly, yet significantly, enhanced after cocaine during both hours of study (p<0.05, p<0.001, respectively) as were ambulations in the SD strain. Nonetheless, the ability for acute cocaine to increase ambulations was significantly greater in SD than in FH animals in the first hour (p<0.001). (4) Central ambulations in the FH strain was not affected by cocaine (both hours, p>0.05), whereas SD animals showed a significant increase in central ambulatory activity in both hours of the cocaine study (p<0.001). The ability for acute cocaine to increase central ambulations was significantly greater in SD than in FH animals (p<0.001). Thus, this is the first study to determine in vivo the neurochemical response to acute cocaine in the behaving FH animal. Moreover, this is the first study to determine in vivo and simultaneously the neurochemical and behavioral response to acute cocaine in the FH strain in comparison with SD animals, a "normal" strain. Remarkable deficiencies in the ability for acute cocaine to alter neurochemistry and behavior in animals with the FH trait are shown. These studies emphasize the need to look differentially at cocaine effects in biochemically and immune-compromised subjects versus "normal" subjects.