Intranasal Administration of Oxytocin Attenuates Social Recognition Deficits and Increases Prefrontal Cortex Inhibitory Postsynaptic Currents following Traumatic Brain Injury

Pediatric TB1 impaired social recognition but not sociability during adolescence. Eleven-day-old male and female rat pups were tested for sociability (stage 2; A, C) and social recognition (stage 3; B, D) at four weeks after injury (adolescent age) using the three-chamber test as described in Materials and Methods. Data are presented as time (in seconds) spent interacting with rat/object (A, B) or as DI (C, D). Open symbols represent sham animals, closed symbols represent injured animals. Bars represent group mean values, and the error bars represent SEM; *p < 0.05.

Pediatric TB1 impaired social recognition but not sociability during adulthood. Eleven-day-old male and female rat pups were tested for sociability (stage 2; A, C) and social recognition (stage 3; B, D) at eight weeks after injury (adult age) using the three-chamber test as described in Materials and Methods. Data are presented as time (in seconds) spent interacting with rat/object (A, B) or as DI (C, D). Open symbols represent sham animals, closed symbols represent injured animals. Bars represent group mean values, and the error bars represent SEM; *p < 0.05.

Brain-injured animals did not exhibit impairments in novel object recognition memory. At four weeks (adolescence, A) and eight weeks (adulthood, B) following injury, sham-injured and brain-injured animals were tested for novel object recognition memory as described in Materials and Methods. The DI was calculated as described in Materials and Methods. Open symbols represent sham animals, closed symbols represent injured animals. Bars represent group mean values, and the error bars represent SEM.

Expression of mRNA for OXT and OXTR in adolescence was not affected following TB1 in 11-d-old rats. After behavioral testing at four to five weeks postinjury, a subset of animals was euthanized and the expression of OXT (A) and OXTR (B) was evaluated in the PVN and mPFC, respectively. Open symbols represent sham animals, closed symbols represent injured animals. Expression (ddCT) values were normalized to sham values. Bars represent group mean values, and the error bars represent SEM.

Intranasal administration of OXT administration reversed social recognition deficits in brain-injured animals in adolescence. At 1 hr before testing animals in the three-chamber test at four after injury, sham-injured and brain-injured animals were administered with saline, OXT at 20 μg, or oxy at 60 μg as described in Materials and Methods. A, Seconds sniffing in stage 2. B, Seconds sniffing in stage 3. C, DI in stage 2. D, DI in stage 3. E, empty cup; R, rat cup; F, familiar rat; N, novel rat. Open symbols represent sham rats, filled symbols represent injured rats, triangles represent vehicle-treated, squares represent 20-μg oxy-treated rats, diamonds represent 60-μg oxy-treated rats; *p < 0.05 in all panels. In panel C, *p < 0.05 compared with brain-injured animals that received saline. Horizontal lines represent group mean values, and the error bars represent SEM.

OXT administration did not affect novelty-induced locomotor activity. At five weeks after brain injury and following testing in the three-chamber test, sham-injured and brain-injured animals were tested for locomotor activity. Animals were administered either saline or OXT 60 μg as described in Materials and Methods.

OXT did not affect membrane properties of Layer II/III pyramidal neurons within the mPFC. Following behavioral testing, slices containing the mPFC were obtained at six to seven weeks after injury and neuronal activity was measured using whole-cell patch clamp electrophysiology as described in Materials and Methods. A, Representative current clamp traces from sham and brain-injured neurons. B, Frequency of neuron firing in response to varying levels of current injection. C, Rheobase. D, Input resistance. E, Membrane voltage. F, Spike threshold. Bars represent mean group values, and error bars represent SEM. Open triangles represent sham cells bathed with aCSF (N = 12), open squares represent sham cells bathed with 1 μm OXT (N = 6), filled triangles represent injured cells bathed with aCSF (N = 13), and filled squares represent injured cells bathed with OXT (N = 10); *p < 0.05.

OXT did not affect spontaneous EPSCs in Layer II/III neurons within the mPFC. A, Representative traces of spontaneous EPSCs recorded from Layer II/III pyramidal neurons within the mPFC. B, Frequency of spontaneous EPSCs. C, Amplitude of spontaneous EPSCs. Bars represent group mean value, and error bars represent SEM. Open triangles represent sham cells bathed with aCSF (N = 16), open squares represent sham cells bathed with 1 μm OXT (N = 11), filled triangles represent injured cells bathed with aCSF (N = 20), filled squares represent injured cells bathed with 1 μm OXT (N = 19).