Cannabinoid administration during adolescence affects various physiological processes, such as motor and affective response, cognitive‐related functions and modulates neurotransmitter activity. Literature remains scant concerning the parallel examination of the effects of adolescent escalating low‐dose Δ9‐tetrahydrocannabinol (Δ9‐THC) on the behavioral and plasticity profile of adult rats in both sexes. Herein, we investigated the long‐term behavioral, neurochemical and neurobiological effects of adolescent escalating low Δ9‐THC doses in adult male and female rats. In adult males, adolescent low‐dose Δ9‐THC exposure led to increased spontaneous locomotor activity, impaired behavioral motor habituation and defective short‐term spatial memory, paralleled with decreased BDNF protein levels in the prefrontal cortex. In this brain area, serotonergic activity was increased, as depicted by the increased serotonin turnover rate, while the opposite effect was observed in the hippocampus, a region where SERT levels were enhanced by Δ9‐THC, compared with vehicle. In adult females, adolescent Δ9‐THC treatment led to decreased spontaneous vertical activity and impaired short‐term spatial memory, accompanied by increased BDNF protein levels in the prefrontal cortex. Present findings emphasize the key role of adolescent escalating low Δ9‐THC exposure in the long‐term regulation of motor response, spatial‐related cognitive functions and neuroplasticity indices in adulthood. In this framework, these changes could, at a translational level, contribute to clinical issues suggesting the development of psychopathology in a sex‐differentiated manner following Δ9‐THC exposure during adolescence.
Background Autonomic responses participate in the pathophysiology of acute myocardial infarction, but their precise time course remains unclear. Here, we investigated the autonomic activity and ventricular tachyarrhythmias in conscious, unrestrained rats post-infarction. Methods The left coronary artery was ligated in 12 Wistar rats, and six rats were sham operated, followed by 24-h electrocardiographic recording via implanted telemetry transmitters. Sympathetic activity was assessed by detrended fluctuation analysis and vagal activity by time- and frequency-domain analysis of heart rate variability. The duration of the ventricular tachyarrhythmias was measured, and voluntary motion served as a marker of heart failure. Results In sham-operated rats, heart rate and sympathetic activity remained low, whereas vagal activity rose progressively after the fourth hour. Post-ligation, medium-sized antero-septal necrosis was observed, reaching ~20% of the left ventricular volume; tachyarrhythmias were frequent, displaying a bimodal curve, and motion counts were low. Vagal activity decreased early post-ligation, coinciding with a high incidence of tachyarrhythmias, but tended to rise subsequently in rats with higher motion counts. Sympathetic activity increased after the third hour, along with a second tachyarrhythmia peak, and remained elevated throughout the 24-h period. Conclusions Vagal withdrawal, followed by gradual sympathetic activation, may participate in arrhythmogenesis during acute myocardial infarction.
Myocardial infarction often leads to progressive structural and electrophysiologic remodeling of the left ventricle. Despite the widespread use of β-adrenergic blockade and implantable defibrillators, morbidity and mortality from chronic-phase ventricular tachyarrhythmias remains high, calling for further investigation on the underlying pathophysiology. Histological and functional studies have demonstrated extensive alterations of sympathetic nerve endings at the peri-infarct area and flow-innervation mismatches that create a highly arrhythmogenic milieu. Such accumulated evidence, along with the previously well-documented autonomic dysfunction as an important contributing factor, has stirred intense research interest for pharmacologic and non-pharmacologic neuromodulation in post-infarction heart failure. In this regard, aldosterone inhibitors, sacubitril/valsartan and sodium-glucose cotransporter type 2 inhibitors have shown antiarrhythmic effects. Non-pharmacologic modalities, currently tested in pre-clinical and clinical trials, include transcutaneous vagal stimulation, stellate ganglion modulation and renal sympathetic denervation. In this review, we provide insights on the pathophysiology of ventricular arrhythmogenesis post-myocardial infarction, focusing on sympathetic activation.
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