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Background/Objectives: Dopamine dysfunction (DA) is a hallmark of many neurological disorders. In this case, the mechanism of changes in dopamine transmission on behavior remains unclear. This study is a look into the intricate link between disrupted DA signaling, neuronal activity patterns, and behavioral abnormalities in a hyperdopaminergic animal model. Methods: To study the relationship between altered DA levels, neuronal activity, and behavioral deficits, local field potentials (LFPs) were recorded during four different behaviors in dopamine transporter knockout rats (DAT-KO). At the same time, local field potentials were recorded in the striatum and prefrontal cortex. Correlates of LFP and accompanying behavioral patterns in genetically modified (DAT-KO) and control animals were studied. Results: DAT-KO rats exhibited desynchronization between LFPs of the striatum and prefrontal cortex, particularly during exploratory behavior. A suppressive effect of high dopamine levels on the striatum was also observed. Wild-type rats showed greater variability in LFP patterns across certain behaviors, while DAT-KO rats showed more uniform patterns. Conclusions: The decisive role of the synchrony of STR and PFC neurons in the organization of motor acts has been revealed. The greater variability of control animals in certain forms of behavior probably suggests greater adaptability. More uniform patterns in DAT-KO rats, indicating a loss of striatal flexibility when adapting to specific motor tasks. It is likely that hyperdopaminergy in the DAT-KO rat reduces the efficiency of information processing due to less synchronized activity during active behavior. [ABSTRACT FROM AUTHOR]

Background/Objectives: Dopamine dysfunction (DA) is a hallmark of many neurological disorders. In this case, the mechanism of changes in dopamine transmission on behavior remains unclear. This study is a look into the intricate link between disrupted DA signaling, neuronal activity patterns, and behavioral abnormalities in a hyperdopaminergic animal model. Methods: To study the relationship between altered DA levels, neuronal activity, and behavioral deficits, local field potentials (LFPs) were recorded during four different behaviors in dopamine transporter knockout rats (DAT-KO). At the same time, local field potentials were recorded in the striatum and prefrontal cortex. Correlates of LFP and accompanying behavioral patterns in genetically modified (DAT-KO) and control animals were studied. Results: DAT-KO rats exhibited desynchronization between LFPs of the striatum and prefrontal cortex, particularly during exploratory behavior. A suppressive effect of high dopamine levels on the striatum was also observed. Wild-type rats showed greater variability in LFP patterns across certain behaviors, while DAT-KO rats showed more uniform patterns. Conclusions: The decisive role of the synchrony of STR and PFC neurons in the organization of motor acts has been revealed. The greater variability of control animals in certain forms of behavior probably suggests greater adaptability. More uniform patterns in DAT-KO rats, indicating a loss of striatal flexibility when adapting to specific motor tasks. It is likely that hyperdopaminergy in the DAT-KO rat reduces the efficiency of information processing due to less synchronized activity during active behavior.

Introduction. Changes in the expression of the dopamine transporter (DAT) have been identified in patients with a number of neuropsychiatric disorders, but their significance for pathogenesis remains unclear. DAT knockout rats are a promising model of frontostriatal dysfunctions involved in adapting learning processes to current organism's needs, motivation, and experience.The objective was to evaluate the effect of DAT disruption on the interaction of classical and instrumental conditioning processes (associative learning).Methods and materials. Rats from a local colony were used: knockouts (n=31), heterozygotes (n=32), and wild type rats (n=24). DAT knockout (Slc6a3) was detected by PCR followed by restriction analysis. The rats were kept individually with limited access to food and unlimited access to water. In the operant chambers equipped with a MED-PC interface (MED Associates, USA), 3 experiments were performed: 1) classical conditioning; 2) autoshaping of operant responding; 3) reward learning based on secondary reinforcement. Statistical analysis was performed using SigmaPlot 12.5 (Systat Software Inc., USA) and SPSS Statistics 21 (IBM, USA).Results. We revealed that DAT disruption in rats did not affect the formation of conditioned reflex connections in classical conditioning (1) but was accompanied by impairments in the autoshaping of the operant response (2) and learning based on secondary reinforcement (3).Conclusion. The observed impairments of associative learning might be associated with a decreased incentive value of stimuli in hyperdopaminergic state.

Early and recent studies show that dopamine through its neuronal systems and receptor subtypes plays different roles in the control of male sexual behavior. These studies show that (i) the mesolimbic/mesocortical dopaminergic system plays a key role in the preparatory phase of sexual behavior, e.g., in sexual arousal, motivation and reward, whereas the nigrostriatal system controls the sensory-motor coordination necessary for copulation, (ii) the incertohypothalamic system is involved in the consummatory aspects of sexual behavior (penile erection and copulation), but evidence for its role in sexual motivation is also available, (iii) the pro-sexual effects of dopamine occur in concert with neural systems interconnecting the hypothalamus and preoptic area with the spinal cord, ventral tegmental area and other limbic brain areas and (iv) D2 and D4 receptors play a major role in the pro-sexual effects of dopamine. Despite some controversy, increases or decreases, respectively, of brain dopamine activity induced by drugs or that occur physiologically, usually improves or worsens, respectively, sexual activity. These findings suggest that an altered central dopaminergic tone plays a role in mental pathologies characterized by aberrant sexual behavior, and that pro-erectile D4 receptor agonists may be considered a new strategy for the treatment of erectile dysfunction in men. [ABSTRACT FROM AUTHOR]

Alterations in dopamine (DA) reuptake are involved in several psychiatric disorders whose symptoms can be investigated in knock out rats for the DA transporter (DAT‐KO). Recent studies evidenced the role of epigenetic DAT modulation in depressive‐like behavior. Accordingly, we used heterozygous (HET) rats born from both HET parents (termed MIX‐HET), compared to HET rats born from WT‐mother and KO‐father (MAT‐HET), implementing the role of maternal care on DAT modulation. We developed a "sudden fright" paradigm (based on dark‐light test) to study reaction to fearful inputs in the DAT‐KO, MAT‐HET, MIX‐HET, and WT groups. Rats could freely explore the whole 3‐chambers apparatus; then, they were gently confined in one room where they experienced the fright; finally, they could freely move again. As expected, after the fearful stimulus only MAT‐HET rats showed a different behavior consisting of avoidance towards the fear‐associated chamber, compared to WT rats. Furthermore, ex‐vivo immuno‐fluorescence reveals higher prefrontal DAT levels in MAT‐HET compared to MIX‐HET and WT rats. Immuno‐fluorescence shows also a different histone deacetylase (HDAC) enzymes concentration. Since HDAC concentration could modulate gene expression, within MAT‐HET fore brain, the enhanced expression of DAT could well impair the corticostriatal‐thalamic circuit, thus causing aberrant avoidance behavior (observed only in MAT‐HET rats). DAT expression seems to be linked to a simply different breeding condition, which points to a reduced care by HET dams for epigenetic regulation. This could imply significant prefronto‐cortical influences onto the emotional processes: hence an excessively frightful response, even to mild stressful agents, may draw developmental trajectories toward anxious and depressed‐like behavior. [ABSTRACT FROM AUTHOR]