Scopolamine but not haloperidol disrupts training-induced neuronal activity in cingulate cortex and limbic thalamus...

Rabbits previously trained to asymptotic performance of discriminative active avoidance behavior (n = 8) received systemic injections of scopolamine hydrobromide (SH: 1.0, 2.0, or 4.0 mg/kg) and scopolamine methylbromide (SM: 4.0 mg/kg). Each rabbit received all of the doses in a counterbalanced order. Single injections were administered 30 min before daily training sessions in which the multi-unit activity in the cingulate cortex and anterior thalamus was recorded. A single session in which saline was administered prior to testing preceded each of the drug sessions, and two days without training followed each drug session to allow dissipation of the drug effects. Additional groups received injections of haloperidol (HA: 0.025, 0.10, or 0.40 mg/kg; n = 7), or both SH/SM and HA (n = 5). The rabbits had been trained to step in an activity wheel in response to a tone CS + to avoid a footshock unconditional stimulus (US), and to ignore a different tone not followed by the US. SH and HA, but not SM, reduced significantly the frequency of conditioned avoidance responses (CRs). All doses of SH significantly attenuated cingulate cortical and AV thalamic training-induced neuronal discharges. HA injections also impaired CR performance but had no effect on the neuronal activity. These results suggest that the loss of the neuronal responses is contributory to the SH-induced CR loss. Absence of an effect of HA on neuronal activity indicates that the HA-induced CR impairment is due to disruption of other neural systems.