Involvement of activation of dopaminergic neuronal system in learning and memory deficits associated with experimental mild traumatic brain injury.
Much evidence has indicated that a disturbance in dopamine neurotransmission following mild to moderate traumatic brain injury is involved in the development of post traumatic memory deficits. In the present study we examined the effects of a dopamine receptor agonist and some antagonists on latent learning and memory deficits associated with a concussive traumatic brain injury in mice. Anaesthetized animals were subjected to mild traumatic brain injury by dropping a weight onto the head, and a single-dose injection of apomorphine (0.3-3.0 mg/kg) or haloperidol (0.3-3.0 mg/kg) was made i.p. 15 min after the trauma. One week later, a water-finding task consisting of an acquisition trial, a retention test and a retest was employed to assess learning and memory functions. Mice that had received a traumatic brain injury were impaired in task performance, with prolonged latencies for finding and drinking in the retention test and retest. Administration of haloperidol but not of apomorphine significantly shortened the prolonged latency in both of the tests, indicating that antagonism of dopamine receptors is beneficial for the recovery of post traumatic memory deficits. In order to evaluate which receptor subtype plays the major role in this model, we examined the effects of SCH-23390 (0.03-0.3 mg/kg), a D1 receptor antagonist, and sulpiride (3.0-30 mg/kg), a D2 receptor antagonist, in the same experimental paradigm. The results showed that administration of sulpiride but not of SCH-23390 significantly improved the deficits in task performance, indicating that D2 receptors are the major site of action. However, combined treatment with SCH-23390 (0.03-0.3 mg/kg) and sulpiride (3.0 mg/kg) at doses that had no effect when the antagonists were given alone exerted a significant additive effect in improving these deficits, indicating that interaction between D1 and D2 receptors is involved in these processes. The present results suggest that a dopaminergic mechanism contributes to the memory dysfunction associated with traumatic brain injury.
Tang
Y P
YP
Department of Neuropsychopharmacology, Nagoya University School of Medicine, Japan.
Noda
Y
Y
Nabeshima
T
T
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D007859:Learning Disabilities / Q000209:etiology*; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000502:physiology*; D012153:Retention, Psychology / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D013469:Sulpiride; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine