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Prevention by the NMDA receptor antagonist, MK801 of neuronal loss produced by tetanus toxin in the rat hippocampus
Author(s) -
Bagetta G.,
Nisticò G.,
Bowery N.G.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14156.x
Subject(s) - tetanus , toxin , medicine , hippocampus , endocrinology , nmda receptor , chemistry , anesthesia , receptor , immunology , biochemistry , vaccination
1 The behavioural and neuropathological effects of tetanus toxin, microinjected directly into the hippocampus, were studied in rats. 2 A single dose (1000 minimum lethal doses, MLDs) of tetanus toxin, injected unilaterally into the hippocampus produced a time‐dependent neuronal loss in the CA1 pyramidal cell layer. In comparison with the contralateral, untreated side these effects became statistically significant ( P > 0.05) 7 days (22.0 ± 1.1% reduction) and 10 days (29.2 ± 1.7% reduction) after the injection. No significant changes were observed 7 days after treatment with 500 MLDs whereas a reduction of 37.5 ± 3.1% in the CA1 area cell number was produced 4 days after the injection of 2000 MLDs. 3 Behavioural stimulatory effects were also induced by tetanus toxin (1000 MLDs) within 48 h of the injection and these culminated in generalized convulsions 5–7 days later. Convulsions were observed after a shorter period of latency in rats receiving 2000 MLDs tetanus toxin whereas 500 MLDs were ineffective. 4 No behavioural and neuropathological effects were observed in rats treated with neutralized tetanus toxin (1000 MLDs), bovine serum albumin or phosphate buffer. 5 Pretreatment with MK801 (0.3 mg kg −1 , i.p., given 1 h before and after the injection with tetanus toxin and then once daily for 4 or 7 days) prevented the behavioural and neuropathological effects induced by tetanus toxin (1000–2000 MLDs). In addition, such treatment fully protected the animals from the lethal effects induced by 1000 MLDs tetanus toxin. By contrast, pretreatment with diazepam (3.0 mg kg −1 , i.p.) using the same schedule as for MK801 did not antagonize the effects of tetanus toxin (1000–2000 MLDs). 6 In conclusion, the present experiments have demonstrated that the intrahippocampal injection of tetanus toxin produces in rats a dose‐ and time‐dependent behavioural stimulation and neuronal loss in the CA1 pyramidal cell layer which can be prevented by the non‐competitive NMDA antagonist, MK801.