RESUMEN
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.
Asunto(s)
Encéfalo/efectos de los fármacos , Trastornos Relacionados con Cocaína/patología , Cocaína/farmacología , Imagen por Resonancia Magnética/métodos , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Sacarosa/administración & dosificación , Animales , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Cocaína/administración & dosificación , Modelos Animales de Enfermedad , Inhibidores de Captación de Dopamina/administración & dosificación , Inhibidores de Captación de Dopamina/farmacología , Ratas , AutoadministraciónRESUMEN
PURPOSE: The interaction between somatosensory cortex and thalamus via a thalamocortical loop is a theory behind induction of absence epilepsy. Inside peri-oral somatosensory (S1po) and primary somatosensory forelimb (S1fl) regions, excitatory and inhibitory systems are not balanced and GABAergic inhibitory synapses seem to play a fundamental role in short-term plasticity alterations. METHODS: We investigated the effects of Ethosuximide on presynaptic changes by utilizing paired-pulse stimulation that was recorded from somatosensory cortex in 18 WAG\Rij rats during epileptic activity. A twisted tripolar electrode including two stimulating electrodes and one recording electrode was implanted into the S1po and S1FL according to stereotaxic landmarks. Paired-pulses (200 µs, 100-1000 µA, 0.1 Hz) were applied to somatosensory cortex at 50, 100, 400, 500 ms inter-pulse intervals for 50 min period. RESULTS: The results showed that paired-pulse facilitation was significantly reduced at all intervals in all times, but compared to the control group of epileptic WAG/Rij rats (p<0.05), it was exceptional about the first 10 minutes after the injection. At the intervals of 50 and 100 ms, a remarkable PPD was found in second, third, fourth and fifth 10-min post injection. CONCLUSION: These experiments indicate that Ethosuximide has effects on presynaptic facilitation in somatosensory cortex inhibitory loops by alteration in GABA levels that leads to a markedly diminished PPF in paired-pulse stimulation.