EFFECTS OF NITRIC OXIDE SYNTHESIS INHIBITION WITH OR WITHOUT NITRIC OXIDE INHALATION ON RESPONSES TO SYSTEMIC COCAINE ADMINISTRATION IN RATS

The effects of Nω-nitro-L-arginine methyl ester(L-NAME)i.v.and nitric oxide(NO) inhalation on integrated systemic responses to cocaine were studied in lightly anesthetized, paralyzed, and mechanically ventilated rats.Cocaine [4 mg/(kg. min) i.v.] produccd seizures then isoelectric electrocephalographic(isoEEG)activity as well as an initial increase in systolic blood pressure and heart rate,then progressive cardiovascular system depression culminating in asystole. Pretreatment with L-NAME[2 mg/(kg. min)i.v. ] for 30 min significantly reduced the incidence of seizure as compared to saline treated animals (saline 7/8; L-NAME 3/8).Doses of cocaine that produced arrhythmias, isoEEG and asystole were significantly lower in the L-NAME treated animals as compared to the saline group. L-NAME did not affect peak systolic blood pressure and heart rate responses to cocaine. NO inhalation(80 ppm)did not affect CNS and cardiovascular responses to cocaine in control animals but enhanced the effects of L-NAME on cocaine toxicity. The results show that pretreatment with L-NAME reduces the central nervous system stimulatory effect of cocaine (reduced seizure incidence) and enhances its depressant effect on both the central nervous system (lower does for isoEEG) and the cardiovascular stimulatory action of cocaine. NO inhalation does not protect against any of the systemic effects of cocaine in animals with normal or suppressed NO production.

Altered relationship between thickness and intrinsic activity amplitude in generalized tonic–clonic seizures

A thinner cortex has higher potential for binding GABA receptor A which is associated with larger amplitudes of intrinsic brain activity(i BA). However, the relationship between cortical thickness and i BA is unknown in intact and epileptic brains. To this end, we investigated the relationship between cortical thickness measured by highresolution MRI and surface-based i BA derived from resting-state functional MRI in normal controls(n = 82) andpatients with generalized tonic–clonic seizures(GTCS)only(n = 82). We demonstrated that the spatial distribution of cortical thickness negatively correlated with surface-based i BA amplitude at both whole-brain and within independent brain functional networks. In GTCS patients,spatial coupling between thickness and i BA amplitude decreased in the default mode, dorsal attention, and somatomotor networks. In addition, the vertex-wise acrosssubject thickness–i BA amplitude correspondence altered in the frontal and temporal lobes as well as in the precuneus in GTCS patients. The relationship between these two modalities can serve as a brain-based marker for detecting epileptogenic changes.