Drug addiction is associated with aberrant memory and permanent functional changes in neural circuits. It is known that exposure to drugs like morphine is associated with positive emotional states and reward-related memory. However, the underlying mechanisms in terms of neural plasticity in the ventral hippocampus, a region involved in associative memory and emotional behaviors, are not fully understood. Therefore, we measured adult neurogenesis, dendritic spine density and brain-derived neurotrophic factor (BDNF) and TrkB mRNA expression as parameters for synaptic plasticity in the ventral hippocampus. Male Sprague Dawley rats were subjected to the CPP (conditioned place preference) paradigm and received 10 mg/kg morphine. Half of the rats were used to evaluate neurogenesis by immunohistochemical markers Ki67 and doublecortin (DCX). The other half was used for Golgi staining to measure spine density and real-time quantitative reverse transcription-polymerase chain reaction to assess BDNF/TrkB expression levels. We found that morphine-treated rats exhibited more place conditioning as compared with saline-treated rats and animals that were exposed to the CPP without any injections. Locomotor activity did not change significantly. Morphine-induced CPP significantly increased the number of Ki67 and DCX-labeled cells in the ventral dentate gyrus. Additionally, we found increased dendritic spine density in both CA1 and dentate gyrus and an enhancement of BDNF/TrkB mRNA levels in the whole ventral hippocampus. Ki67, DCX and spine density were significantly correlated with CPP scores. In conclusion, we show that morphine-induced reward-related memory is associated with neural and synaptic plasticity changes in the ventral hippocampus. Such neural changes could underlie context-induced drug relapse.

Synchronization of bioelectrical activities of neurons contributes to the initiation of epileptiform activities occurred during a seizure attack. Absence seizures are characterized by synchronous and symmetric 2.5-4 Hz spike-wave discharges in children under 15 years old. More than half of children with absence epilepsy suffer from cognitive, education, and learning difficulties. The amplitude ratio of the theta and alpha waves is a reliable indicator for measuring of learning difficulties in children. The aim of this study was to evaluate the effect of Land T-type voltage-dependent calcium channel blockers, verapamil and ethosuximide, on the amplitude of electroencephalogram (EEG) waves in WAG/Rij rats, a genetic animal model of absence epilepsy. Materials and Methods: 18 adult WAG/Rij rats in the age between 4 and 6 months were divided randomly into 3 groups. Using stereotaxic method, cannula was implanted in the peri-oral region of the primary somatosensory cortex for injection of drugs and recording electrodes were placed in the frontal and the occipital cortices. Electroencephalography was recorded 30 minutes before and one hour after drug injection. Results: The power of EEG sub-bands significantly decreased in the first 30 minutes after injection of verapamil and ethosuximide compared to the control group. Conclusion: Our data show that verapamil and ethosuximide can decrease the power of EEG sub-bands. However, they have not noticeable effect on theta to alpha ratio.

Excessive use of cocaine is known to induce changes in brain white and gray matter. It is unknown whether the extent of these changes is related to individual differences in vulnerability to cocaine addiction. One factor increasing vulnerability involves reduced expression of the serotonin transporter (5‐HTT). Human studies have shown that inherited 5‐HTT downregulation is associated with structural changes in the brain. These genotype‐related structural changes may contribute to risk for cocaine addiction. Here, we tested this idea by using ultrahigh‐resolution structural magnetic resonance imaging (MRI) on postmortem tissue of 5‐HTT−/− and wild‐type (5‐HTT+/+) rats with a history of long access to cocaine or sucrose (control) self‐administration. We found that 5‐HTT−/− rats, compared with wild‐type control animals, self‐administered more cocaine, but not sucrose, under long‐access conditions. Ultrahigh‐resolution structural MRI subsequently revealed that, independent of sucrose or cocaine self‐administration, 5‐HTT−/− rats had a smaller amygdala. Moreover, we found an interaction between genotype and type of reward for dorsal raphe nucleus volume. The data point to an important but differential role of the amygdala and dorsal raphe nucleus in 5‐HTT genotype–dependent vulnerability to cocaine addiction.

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