Perinatal Lead Exposure Causes Increased Sensitivity to Aversive Conditioning in Rat’s: Implications for Lower Sensory Thresholds for Emotional Learning and Memory Tasks

Abstract

Lead is well-established neurotoxin that causes brain damage to the developing brain with persistent effects that remain across the lifespan. Dependent upon the developmental time-period of exposure (e.g., gestation, perinatal, or postnatal), lead may cause selective disruption of either the excitatory NMDAR-dependent or inhibitory GABAR-dependent neural circuitry. This suggests that lead exposure may cause very different developmental neuropathologies, that in turn, produce altered neuroadaptations to sensory and other contextual stimuli. In order to test this theory, rats that were treated with lead (150 ppm lead acetate perinatally) and compared to control rats (0 ppm) and subjected to an Open Field test (OF), an Elevated Plus Maze test (EPM), and an Active Avoidance Test (AAT). The OF data showed that lead treatment reduced locomotor activity and speed irrespective of sex when compared to control rats. The EPM data showed that selective anxiety-like behaviors induced by lead in female rats, but not male rats when compared to control rats. The AAT revealed that lead induced enhanced learning across both sexes, but the female rat’s avoidance and escape behaviors were greater than the lead male rats. The lead treated rats learned the AAT better than the control rats, not due to intellectual capacity but rather due to an altered and enhanced sensitivity to the aversive stimulus (i.e., foot shock). This suggests that perinatal lead exposure disrupts the early programming of the emotional regulatory neural systems within the limbic system (i.e., consistent with the GABA-shift), and as a result, causes sensory enhancement to aversive/noxious stimuli similar to a model of childhood post-traumatic stress disorder (PTSD) with anxiety-like symptoms.