Effects of psychological stressors and [delta]⁹-THC acutely and chronically on zebra finch song behavior and dendritic spine density

Abstract

This dissertation investigated song performance and dendritic spine density, following acute restraint stress in adult zebra finches and, following chronic mild stress and CB1 receptor partial agonist [delta]⁹-tetrahydrocannabinol ( [delta]⁹-THC) treatments (3 mg/kg) during sensorimotor development or adulthood. CB1 receptor agonists and stressors have mechanistic overlap: a stressor activates glucocorticoid corticosterone release in the hypothalamic-pituitary-adrenal axis, and endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are CB1 receptor agonists which operate as an endogenous stress buffer system that turns off the response. The endocannabinoid system is prominent during late postnatal development and may modulate important synaptic fine-tuning. Chronic CB1 receptor agonist treatment or stressors during this developmental stage may disrupt appropriate endocannabinoid signaling mediating brain development. Male zebra finches possess a developmental, sensorimotor critical period for learning a song in a mechanism similar to language acquisition in humans. Initially in sensorimotor development, zebra finches possess a surplus of dendritic spines, which are the anatomical basis of the post-synaptic site with excitatory input and may represent morphological building blocks of learning and memory. Over time, a net elimination occurs as part of the developmental learning process. In this dissertation, acute restraint stress (30 minutes) in adults rapidly increased plasma corticosterone levels, altered performance of spectral and temporal acoustic features, and stimulated dendritic spine and c-Fos immunolabeled nuclei density in higher-order acoustic region NCM. [delta]⁹-THC, the principal psychoactive component of marijuana, inhibits perceptual sensory processing, and [delta]⁹-THC pretreatment antagonized the effects of stress on c-Fos density in NCM in a CB1 receptor inverse agonist/antagonist SR141716 (6 mg/kg)-reversible manner. The acute effects differed from chronic effects. In adult groups, chronic mild stress or [delta]⁹-THC treatments alone did not alter corticosterone levels, song acoustic features, or dendritic spine density in NCM or basal ganglia/striatal region Area X. Both chronic stress and [delta]⁹-THC treatments during sensorimotor song development resulted in effects persistent into adulthood, with reduced syllable entropy and dendritic spine density in Area X. These effects suggest an interference with typical developmental song learning and brain development. Adolescent brain development may be vulnerable to long-term consequences following chronic exposure to CB1 receptor agonists or stressors, and their effects likely differ than exposure during adulthood. This distinction is important to the elucidation of mechanisms and outcomes of marijuana and psychological disorders, such as depression.