Effects of chronic antidepressant drug administration and electroconvulsive shock on activity of dopaminergic neurons in the ventral tegmentum: a reply to Chenu

We have read the letter commenting on our article entitled ‘Effects of chronic antidepressant drug administration and electroconvulsive shock on activity of dopaminergic neurons in the ventral tegmentum’. We offer the following response. The authors of the letter direct attention to our mean spontaneous firing rate for dopaminergic neurons in the ventral tegmental area (VTA-DA neurons) being lower than typically found and particularly note that we included neurons with firing rates as low as 1.0 Hz. Our mean rates of firing are indeed somewhat lower than often reported by other investigators. We were clearly aware of this, specifically describing in our Methods section that we included slow-firing neurons. Our criteria for DA neurons in the VTA depended upon (a) stereotaxic location and then (b) the specific wave form of the unit as stated in the Procedure section, which is widely acknowledged for these neurons. Because we were recording multiple neurons in each animal, there was no way to mark individual neurons and identify their locations and/or characteristics histologically ; consequently, we included neurons based on waveform. Given these criteria, we saw no basis for discarding neurons because their firing rate was slow and, consequently, such neurons were included. The writers of the letter call attention to an article by Ungless et al. (2004), who described differences between DA and non-DA neurons in the VTA. The writers noted that our mean spontaneous firing rate was closer to that of non-dopaminergic cells than dopaminergic cells. However, the main point of the article by Ungless et al. was that VTA-DA neurons were inhibited by aversive or stressful stimuli whereas non-DA neurons were excited by such stimuli ; they reported 10 of 12 DA neurons were inhibited by 10-s foot pinch whereas four of six non-DA neurons were excited by this stimulus. We have examined the effects of foot pinch on VTA-DA cell activity, using our standard paw compression (PC) of 1.0 s duration that elicits sensory-evoked burst firing of locus coeruleus (LC) neurons. In a study of normal rats and one of our selectively bred rat lines, we recorded from a total of 170 VTA-DA units ; for each unit, response to PC was determined. Of the 170 units, spontaneous firing of 103 units was clearly inhibited by PC, while four units showed excitation. (Incidentally, this study was carried out and completely scored prior to our seeing the findings of Ungless et al., so these results could not have been biased by their findings.) Thus, the ‘inhibition versus excitation criteria’ of Ungless et al. indicates that we record overwhelmingly from DA neurons in the VTA. Finally, on some occasions (although not often), we have injected apomorphine at the conclusion of an experiment and observed that this shut down the activity of putative VTA-DA neurons, as would be expected from dopaminergic units. We continue to believe that, regardless of our mean rate of firing having been somewhat lower than that reported by others, we still have no basis for excluding neurons that meet appropriate criteria. In regard to rate of firing, we have observed that neurons in different regions of the VTA have different firing rates. In particular, a horizontal band of VTADA neurons near the ventral limit of the VTA characteristically fires at a high rate (4–5 Hz or higher) and a high percentage of spikes in bursts. If one were to focus on this subpopulation, the average firing rate indeed would be higher than the values we reported. Without a detailed histological analysis, it is impossible to know the extent to which this scenario might explain apparent discrepancies. Other possibilities that might explain differences in firing rate relate to the particular animals we use. Our Address for correspondence: J. M. Weiss, Ph.D., Emory University School of Medicine, Emory West Campus, Building A, Room 510-N, 1256 Briarcliff Road, N. E., Atlanta, GA 30306, USA. Tel. : 404-712-9771 Fax : 404-712-9755 Email : [email protected] International Journal of Neuropsychopharmacology (2012), 15, 555–557. f CINP 2011 doi:10.1017/S1461145711001726 LETTER TO THE EDITOR