General anesthetic exposure in adolescent rats causes persistent maladaptations in cognitive and affective behaviors and neuroplasticity

• Published in: Neuropharmacology 2019-05, Vol.150, p.153-163
• Main Authors: Landin, Justine D., Palac, Magdalena, Carter, Jenna M., Dzumaga, Yvette, Santerre-Anderson, Jessica L., Fernandez, Gina M., Savage, Lisa M., Varlinskaya, Elena I., Spear, Linda P., Moore, Scott D., Swartzwelder, H. Scott, Fleming, Rebekah L., Werner, David F.
• Format: Article
• Language: English
• Subjects: Adolescence; Affect - drug effects; Anesthesia; Anesthetics, General - pharmacology; Animals; Anxiety; Behavior, Animal - drug effects; Cognition - drug effects; Dendritic Spines - drug effects; Exploratory Behavior - drug effects; GABA; Impulsive Behavior - drug effects; Impulsivity; Isoflurane; Isoflurane - pharmacology; Male; Memory; Neuronal Plasticity - drug effects; Neuroplasticity; Prefrontal Cortex - drug effects; Pyramidal Cells - drug effects; Rats; Rats, Sprague-Dawley
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2019.03.022

Accumulating evidence indicates that exposure to general anesthetics during infancy and childhood can cause persistent cognitive impairment, alterations in synaptic plasticity, and, to a lesser extent, increased incidence of behavioral disorders. Unfortunately, the developmental parameters of susceptibility to general anesthetics are not well understood. Adolescence is a critical developmental period wherein multiple late developing brain regions may also be vulnerable to enduring general anesthetic effects. Given the breadth of the adolescent age span, this group potentially represents millions more individuals than those exposed during early childhood. In this study, isoflurane exposure within a well-characterized adolescent period in Sprague-Dawley rats elicited immediate and persistent anxiety- and impulsive-like responding, as well as delayed cognitive impairment into adulthood. These behavioral abnormalities were paralleled by atypical dendritic spine morphology in the prefrontal cortex (PFC) and hippocampus (HPC), suggesting delayed anatomical maturation, and shifts in inhibitory function that suggest hypermaturation of extrasynaptic GABAA receptor inhibition. Preventing this hypermaturation of extrasynaptic GABAA receptor-mediated function in the PFC selectively reversed enhanced impulsivity resulting from adolescent isoflurane exposure. Taken together, these data demonstrate that the developmental window for susceptibility to enduring untoward effects of general anesthetics may be much longer than previously appreciated, and those effects may include affective behaviors in addition to cognition. •Adolescence is a critical developmental period, during which the consequential effects of general anesthetics are not known.•Results suggest that adolescent anesthetic exposure enduringly alters cognition, impulsivity and anxiety related behaviors.•Adolescent anesthetic exposure also altered neuronal morphology, physiological inhibitory function.•Results further inform developmental anesthetic vulnerability to psychiatric disorders that precipitate during adolescence.