Mild to moderate traumatic brain injury (TBI) is associated with enduring impairments of cognitive function in both humans and animals. However, few experiments have investigated the role of post-injury pharmacologic strategies for attenuating the observed cognitive impairment after TBI. This investigation examined the effects of selective blockade of the presynaptic muscarinic M2 autoreceptor with BIBN 99 on cognitive recovery following rodent TBI. Experiment 1 investigated the effects of delayed post-injury administration of BIBN 99 on cognitive performance following moderate central fluid percussion TBI (2.1 +/- 0.05 atm). On days 11-15 after injury-cognitive performance was assessed with a Morris water maze (MWM) task. One hour before MWM testing injured rats were injected (s.c.) with either vehicle (n = 9), 0.5 (n = 8), or 1.0 (n = 8) mg/kg of BIBN 99. Results indicated that injured rats receiving the delayed post-injury treatment with BIBN 99 performed no better than injured-vehicle treated rats. In experiment 2, injured rats were injected (s.c.) once daily with either vehicle (n = 9), 0.5 (n = 9), or 1.0 (n = 9) mg/kg of BIBN 99 throughout the duration of the experiment beginning 24 h after TBI. Sham-injured animals injected (s.c.) with vehicle (n = 9) or 1.0 (n = 8) mg/kg of BIBN 99 were included for comparison. On days 11-15 after injury, cognitive performance was assessed with the MWM procedure. Results of the second experiment indicated that both doses of BIBN 99 were effective in attenuating cognitive deficits in the MWM as compared to the injured-vehicle treated animals (P < 0.05 for both comparisons).(ABSTRACT TRUNCATED AT 250 WORDS)