Mild traumatic lesion of the right parietal cortex in the rat: characterisation of a conditioned freezing deficit and its reversal by dizocilpine.
We have previously demonstrated that traumatic injury of the lateral aspect of the right parietal cortex results in reduced acquisition of the passive avoidance task but enhanced learning in an active avoidance procedure. In order to try to explain the apparent dichotomy between these findings a series of experiments examined the effect of fluid percussion-induced traumatic brain injury (FP-TBI) on the conditioned freezing response to a context previously paired with an aversive stimulus. Rats subjected to FP-TBI displayed less conditioned freezing than the sham-operated controls. This effect was particularly marked when the delay between context exposure and footshock was short (< or = 30 s) and was no longer significant when this delay was 3 min, indicating that the injured animals did not have an impaired freezing response per se. This phenomenon was enduring such that it could still be observed 2 months following the surgery. There was no significant freezing deficit after FP-TBI of the motor cortex, demonstrating that the site of injury is important and that the freezing deficit is not a general response to CNS trauma. The NMDA receptor antagonist dizocilpine (MK-801, 1 mg/kg i.v.) significantly reduced the trauma-induced freezing deficit when administered as a single bolus 15 min prior to the surgery, or as three repeated treatments (3 x 0.33 mg/kg) 15 min, and 6 and 24 h following lesion. The trauma-induced deficit in conditioned freezing can explain the differences in active and passive avoidance behaviours and appears to be specific to lesion of the lateral parietal cortex. In addition, the behavioural deficit can be attenuated using the neuroprotective agent dizocilpine, suggesting that it may prove useful as a sensitive and specific measure of cortical damage following traumatic injury.
Hogg
S
S
Synthélabo Recherche, Rueil-Malmaison, France.
Sanger
D J
DJ
Moser
P C
PC
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000523:psychology*; D003214:Conditioning, Classical / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007103:Immobilization; D008297:Male; D009044:Motor Cortex / Q000293:injuries; D010296:Parietal Lobe / Q000293:injuries*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate