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Sex-specific brain deficits in auditory processing in an animal model of cocaine-related schizophrenic disorders.

Broderick PA, Rosenbaum T - Brain Sci (2013)

Bottom Line: The startle method operates through auditory pathways in brain via a network of sensorimotor gating processes within auditory cortex, cochlear nuclei, inferior and superior colliculi, pontine reticular nuclei, in addition to mesocorticolimbic brain reward and nigrostriatal motor circuitries.Key findings are: (a) Cocaine significantly reduced PPI in both sexes. (b) Females were significantly more sensitive than males; reduced PPI was greater in females than in males. (c) Physiological saline had no effect on startle in either sex.The data further suggest that hormones may play a role in these sex differences to acoustic startle reported herein.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Pharmacology & Neuroscience, The Sophie Davis School of Biomedical Education, The City College of New York, The City University of New York, New York, NY 10031, USA. broderick@med.cuny.edu.

ABSTRACT
Cocaine is a psychostimulant in the pharmacological class of drugs called Local Anesthetics. Interestingly, cocaine is the only drug in this class that has a chemical formula comprised of a tropane ring and is, moreover, addictive. The correlation between tropane and addiction is well-studied. Another well-studied correlation is that between psychosis induced by cocaine and that psychosis endogenously present in the schizophrenic patient. Indeed, both of these psychoses exhibit much the same behavioral as well as neurochemical properties across species. Therefore, in order to study the link between schizophrenia and cocaine addiction, we used a behavioral paradigm called Acoustic Startle. We used this acoustic startle paradigm in female versus male Sprague-Dawley animals to discriminate possible sex differences in responses to startle. The startle method operates through auditory pathways in brain via a network of sensorimotor gating processes within auditory cortex, cochlear nuclei, inferior and superior colliculi, pontine reticular nuclei, in addition to mesocorticolimbic brain reward and nigrostriatal motor circuitries. This paper is the first to report sex differences to acoustic stimuli in Sprague-Dawley animals (Rattus norvegicus) although such gender responses to acoustic startle have been reported in humans (Swerdlow et al. 1997 [1]). The startle method monitors pre-pulse inhibition (PPI) as a measure of the loss of sensorimotor gating in the brain's neuronal auditory network; auditory deficiencies can lead to sensory overload and subsequently cognitive dysfunction. Cocaine addicts and schizophrenic patients as well as cocaine treated animals are reported to exhibit symptoms of defective PPI (Geyer et al., 2001 [2]). Key findings are: (a) Cocaine significantly reduced PPI in both sexes. (b) Females were significantly more sensitive than males; reduced PPI was greater in females than in males. (c) Physiological saline had no effect on startle in either sex. Thus, the data elucidate gender-specificity to the startle response in animals. Finally, preliminary studies show the effect of cocaine on acoustic startle in tandem with effects on estrous cycle. The data further suggest that hormones may play a role in these sex differences to acoustic startle reported herein.

No MeSH data available.


Related in: MedlinePlus

(Fall, Group A) (n = 6) shows the effect of cocaine on females (left) and males (right). Statistically significant differences occurred in the interaction between and within dosage.
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brainsci-03-00504-f002: (Fall, Group A) (n = 6) shows the effect of cocaine on females (left) and males (right). Statistically significant differences occurred in the interaction between and within dosage.

Mentions: Group A (Figure 2) showed statistically significant differences in the dose response interaction of cocaine in females and males (F(2,12) = 11.15, p < 0.002). In Group A, in females and males, the 20 mg/kg dose of cocaine showed a maximum effect in pre-pulse attenuation of acoustic startle. Group B (Figure 3) female versus male analysis showed dosage × gender interaction significance (F(2,12) = 6.81 and p < 0.01). Gender alone significance was analyzed, significance was found (F(1,12) = 11.90, p < 0.005). Cocaine dosage alone was significant as well (F(2,12) = 8.00, p < 0.006). In Group B, in females, the 20 mg/kg i.p. dose of cocaine resulted in a maximum attenuation of pre-pulse inhibition in the injection test. The within gender data gave the following results; Group A males versus Group B males showed between group significance, male × male (F(1,12) = 14.91, p < 0.002). Group A females with Group B females, females × females, showed cocaine dosage significance; (F(2,12) = 15.76, p < 0.0004).


Sex-specific brain deficits in auditory processing in an animal model of cocaine-related schizophrenic disorders.

Broderick PA, Rosenbaum T - Brain Sci (2013)

(Fall, Group A) (n = 6) shows the effect of cocaine on females (left) and males (right). Statistically significant differences occurred in the interaction between and within dosage.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061862&req=5

brainsci-03-00504-f002: (Fall, Group A) (n = 6) shows the effect of cocaine on females (left) and males (right). Statistically significant differences occurred in the interaction between and within dosage.
Mentions: Group A (Figure 2) showed statistically significant differences in the dose response interaction of cocaine in females and males (F(2,12) = 11.15, p < 0.002). In Group A, in females and males, the 20 mg/kg dose of cocaine showed a maximum effect in pre-pulse attenuation of acoustic startle. Group B (Figure 3) female versus male analysis showed dosage × gender interaction significance (F(2,12) = 6.81 and p < 0.01). Gender alone significance was analyzed, significance was found (F(1,12) = 11.90, p < 0.005). Cocaine dosage alone was significant as well (F(2,12) = 8.00, p < 0.006). In Group B, in females, the 20 mg/kg i.p. dose of cocaine resulted in a maximum attenuation of pre-pulse inhibition in the injection test. The within gender data gave the following results; Group A males versus Group B males showed between group significance, male × male (F(1,12) = 14.91, p < 0.002). Group A females with Group B females, females × females, showed cocaine dosage significance; (F(2,12) = 15.76, p < 0.0004).

Bottom Line: The startle method operates through auditory pathways in brain via a network of sensorimotor gating processes within auditory cortex, cochlear nuclei, inferior and superior colliculi, pontine reticular nuclei, in addition to mesocorticolimbic brain reward and nigrostriatal motor circuitries.Key findings are: (a) Cocaine significantly reduced PPI in both sexes. (b) Females were significantly more sensitive than males; reduced PPI was greater in females than in males. (c) Physiological saline had no effect on startle in either sex.The data further suggest that hormones may play a role in these sex differences to acoustic startle reported herein.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Pharmacology & Neuroscience, The Sophie Davis School of Biomedical Education, The City College of New York, The City University of New York, New York, NY 10031, USA. broderick@med.cuny.edu.

ABSTRACT
Cocaine is a psychostimulant in the pharmacological class of drugs called Local Anesthetics. Interestingly, cocaine is the only drug in this class that has a chemical formula comprised of a tropane ring and is, moreover, addictive. The correlation between tropane and addiction is well-studied. Another well-studied correlation is that between psychosis induced by cocaine and that psychosis endogenously present in the schizophrenic patient. Indeed, both of these psychoses exhibit much the same behavioral as well as neurochemical properties across species. Therefore, in order to study the link between schizophrenia and cocaine addiction, we used a behavioral paradigm called Acoustic Startle. We used this acoustic startle paradigm in female versus male Sprague-Dawley animals to discriminate possible sex differences in responses to startle. The startle method operates through auditory pathways in brain via a network of sensorimotor gating processes within auditory cortex, cochlear nuclei, inferior and superior colliculi, pontine reticular nuclei, in addition to mesocorticolimbic brain reward and nigrostriatal motor circuitries. This paper is the first to report sex differences to acoustic stimuli in Sprague-Dawley animals (Rattus norvegicus) although such gender responses to acoustic startle have been reported in humans (Swerdlow et al. 1997 [1]). The startle method monitors pre-pulse inhibition (PPI) as a measure of the loss of sensorimotor gating in the brain's neuronal auditory network; auditory deficiencies can lead to sensory overload and subsequently cognitive dysfunction. Cocaine addicts and schizophrenic patients as well as cocaine treated animals are reported to exhibit symptoms of defective PPI (Geyer et al., 2001 [2]). Key findings are: (a) Cocaine significantly reduced PPI in both sexes. (b) Females were significantly more sensitive than males; reduced PPI was greater in females than in males. (c) Physiological saline had no effect on startle in either sex. Thus, the data elucidate gender-specificity to the startle response in animals. Finally, preliminary studies show the effect of cocaine on acoustic startle in tandem with effects on estrous cycle. The data further suggest that hormones may play a role in these sex differences to acoustic startle reported herein.

No MeSH data available.


Related in: MedlinePlus