Search

This study examined the delayed effects of the administration of d-amphetamine, methoxamine (an alpha1-adrenergic receptor agonist), and prazosin (an alpha1-adrenergic receptor antagonist) on the behavioral outcome of lateral fluid-percussion (FP) brain injury. Rats trained to perform a beam-walking task were subjected to brain injury of moderate severity (2.1 to 2.2 atm). Twenty-four hours after injury, rats were treated with amphetamine, methoxamine, or prazosin at two or three different dose levels. Amphetamine-treated animals displayed no significant improvement in beam-walking ability either during or after drug intoxication (from days 3 to 5 after brain injury). Similarly, neither methoxamine nor prazosin significantly affected beam-walking ability during or after drug intoxication. Neither amphetamine treatment at three different doses nor treatment with methoxamine or prazosin at two different doses affected the spatial learning disabilities of brain-injured animals. These results suggest that (1) unlike amphetamine administration after sensorimotor cortex (SMC) ablation or contusion brain injury models, amphetamine administration at 24 h after concussive FP brain injury does not improve beam-walking performance; (2) unlike amphetamine administration 10 min after concussive FP brain injury amphetamine administration 24 h after injury does not improve cognitive function; and (3) unlike prazosin administration after SMC ablation brain injury, prazosin administration 24 h after concussive FP brain injury does not effect beam-walking performance.

Regional concentrations of leukotriene C4 and extravasation of Evans blue were measured after lateral fluid-percussion brain injury in rats. Tissue levels of LTC4 were elevated in the injured cortex at 10 min, 30 min, and 1 h after injury; these levels returned to normal by 2 h after injury. Increases in the levels of LTC4 were also observed in the ipsilateral hippocampus after brain injury, and these elevations persisted for 2 h after injury. No significant increase in levels of LTC4 was observed in the contralateral cortex at any time after injury. A substantial extravasation of Evans blue was observed only in the ipsilateral cortex and hippocampus at 3 h and 6 h after brain injury. Although a temporal association between LTC4 and blood-brain barrier (BBB) breakdown is suggested by these data, no cause-and-effect relationship has been addressed in this study. However, it is possible that, as is true for cerebral ischemia, LTC4 may play a role as a mediator in the BBB breakdown associated with fluid-percussion brain injury in rats.

The physiological and behavioral effects of embryonic exposure to ethanol and cocaine, given during active neurogenesis (embryonic days E3 and E4), were studied in 1- and 2-day-old chicks. Broiler chicks (n = 131) from five embryonic treatment conditions were tested: incubative controls (n = 28), vehicle (saline plus 50 micrograms/ml bacitracin; n = 27), 10 mg ethanol (n = 20), 150 micrograms cocaine (n = 25), or co-drug (10 mg ethanol and 150 micrograms cocaine; n = 31). Compared with controls, embryo mortality for the cocaine alone embryos was significantly increased. No significant embryonic treatment effects among chicks were found for hatching times, body weights at hatch and testing, and temperature regulation when cold stressed. Behaviorally, chicks were first trained to key-peck for heat/light reward (autoshaping). Chicks in all groups increased responding from autoshape session 1 to session 2 (24 trials/session). In an acquisition-extinction session (12 trials/phase), chicks in all groups except those in the co-drug group decreased responding from acquisition to extinction. In a second acquisition-extinction session following a drug challenge of 0.5 mg/kg apomorphine, chicks in all embryonic treatment groups showed enhanced responding. Hence, in those chicks that survived, the selected doses of ethanol and cocaine produced minimal physiological and behavioral effects individually, but when given together did produce a significant deficit in extinction responding.