Activity of A9 and A10 dopaminergic neurons in unrestrained rats: further characterization and effects of apomorphine and cholecystokinin.

The activity of single dopaminergic (DA) neurons (total n = 77) in the midbrain of awake, unrestrained rats was examined. The firing rates and patterns of ventral tegmental area (A10) cells (n = 39) were similar to those of identified DA neurons in anesthetized and paralyzed rats. Unit activity was briefly stimulated (increased firing rate and burst activity) in response to an auditory stimulus and during manual stimulation of the vibrissae. Similar changes occurred during orienting responses and periods of sniffing. Twenty-six percent of A10 cells recorded appeared to be electronically coupled which matched the prevalence previously observed among A9 neurons. The effects on A9 and A10 DA cell activity of apomorphine and the carboxyterminal octapeptide of cholecystokinin (CCK-8) were then determined. Sequential doses of apomorphine (5-320 micrograms/kg, i.v.) reduced the firing rate of each neuron tested (n = 19). Ten of these cells were classified as 'sensitive' to the drug (ED50 less than 20 micrograms/kg), while the remainder were considerably 'less sensitive' (ED50 greater than 30 micrograms/kg). Cells of either sensitivity were as likely to be found in A9 as in A10. Sulfated CCK-8 (1-16 micrograms/kg, i.v.) excited (firing rate and bursting increased) 73% of the A9 neurons sampled but produced inconsistent effects on A10 cell firing. CCK-8 pretreatment increased the percentage of A9 and A10 neurons which were classified as 'sensitive' to apomorphine (82%). Enhanced sensitivity to apomorphine occurred regardless of the effect of CCK-8 on unit firing. Thus, as has been found in anesthetized rats, CCK-8 appeared to enhance the inhibitory effects of a DA agonist on DA neurons.