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Rats were trained to stable performance in a conditional brightness discrimination task and then received infusions of ibotenic acid or vehicle into the basal forebrain. Following 2 weeks of recovery, animals were retested in the original discrimination. Lesioned rats tended to performed badly on the first day of testing as measured by all parameters (percent correct responding, latency to respond, and missed trials) but thereafter, most rats recovered quickly to prelesion levels. In keeping with previous reports, an approximately 30% reduction in choline acetyltransferase activity was observed in the lesioned animals. Four rats showed no recovery over a period of several months; however, an analysis of the choline acetyltransferase in several brain regions revealed no obvious differences to those animals in which performance recovered. Postlesion testing with the putative nootropic β-carboline ZK 93426 showed no major differences to the effects observed in control animals. Scopolamine had similar negative effects in both groups tested. These data indicate that deficits induced by lesions of the basal forebrain do not correlate with reductions in cholinergic activity.

Drug addicts abusing heroin substitutes contaminated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and perhaps those who work with this substance, may develop symptoms similar to those seen in Parkinson's disease [7, 12, 13]. We describe the results of a study in which rats were given daily injections of MPTP for two weeks. A progressive suppression of activity was seen, but the subjects rapidly recovered when treatment ceased. The animals were then injected with d -amphetamine or apomorphine; the former drug enhanced activity, to levels seen in control (non-MPTP treated) subjects. Apomorphine had no effect, either on control or MPTP-treated subjects. The effects of acute (0, 2.5, 5.0 and 10.0 mg per rat) administration of MPTP were also studied. The two lower doses significantly decreased activity, but the highest dose did not. Histological examination showed that 2 weeks' treatment with MPTP did not produce neuronal degeneration in the pars compacta of the substantia nigra (SN). In these animals, there were no changes in levels of dopamine, 5-hydroxytryptamine, or their metabolites in either the SN or the caudate nucleus. MPTP had no effect on the levels of neurotensin, somatostatin and substance P in several brain areas. It is concluded that MPTP has reliable effects on locomotor activity in rats without producing measurable histological or neurochemical changes in the nigrostriatal dopaminergic system.