Louis R. Lucas
Ph.D. 1993, Tulane University
My research interests focus mainly on understanding the neural substrates of motivated behaviors and the interplay between hormones and the brain. For this purpose, I have used a number of behavioral paradigms including several using drug abuse susceptibility, another with ingestive behaviors, and yet another using a social stress animal model. What my colleagues and I have discovered thus far is that a key brain system, consisting of mesolimbic connections, plays a pivotal role in the execution in all of these behaviors. Furthermore, the informational exchange between the periphery, as transmitted though hormones, and the brain, as possibly mediated through neuropeptidergic systems, determines the overt behavior that the model is studying. Future research plans include testing the hypothesis that while catecholamines and excitatory/inhibitory systems are involved in the processing of the motivated state, long term changes in behavior are accomplished through the modulation of neuropeptidergic systems that are themselves modified through feedback interactions with systemic hormones.
Lucas LR, Dragisic T, Duwaerts CC, Swiatkowski M, Suzuki H. Effects of recovery from immobilization stress on striatal preprodynorphin- and kappa opioid receptor-mRNA levels of the male rat. Physiology & Behavior 2011 (in press).
Suzuki H, Han SD, Lucas LR. Increased 5-HT1b receptor density in the basolateral amygdala of passive observer rats exposed to aggression Brain Research Bulletin 83(1-2), 38-43 (2010).
Suzuki H, Han SD, Lucas LR. Chronic passive exposure to aggression decreases D2 and 5-HT1b receptor densities Physiology & Behavior 99(5):562-70 (2010).
Aher CV, Duwaerts CC, Akama KT, Lucas LR. Effects of acute diuresis stress on egr-1 (zif268) mRNA levels in brain regions associated with motivated behavior Brain Research Bulletin 81:114-119 (2009).
Suzuki H, Lucas LR. Chronic passive exposure to aggression escalates aggressiveness of rat observers Aggressive Behavior 35:1-13 (2009).
L.R. Lucas, C.-J. Wang, T. M. McCall, and B.S. McEwen. 2007. Effects of immobilization stress on neurochemical markers of dopamine activity in the motivational system of the male rat. Brain Research 1155:108-115.
Lucas LR, Grillo CA, McEwen BS. 2007. Salt appetite in sodium-depleted or sodium-replete conditions: Possible role of opioid receptors. Neuroendocrinology, 85(3), 139 - 147.
Lucas L.R., Celen Z, Tamashiro K.L., Blanchard R.J., Blanchard D.C., Markham C, Sakai R.R., McEwen B.S. 2004. Repeated exposure to social stress has long-term effects on indirect markers of dopaminergic activity in brain regions associated with motivated behavior. Neuroscience 124:449-57.
Lucas L.R., Grillo C.A., and McEwen B.S. 2003. Salt appetite in furosemide treated salt-depleted rats: involvement of the mesolimbic neuropeptide system in salt craving behavior. Neuroendocrinology 77:406-415.
Lucas L.R., Reagan L.P., Akama K.T., Ma L.-Y., Tamashiro K.L.K., Sakai R.R. and McEwen B.S. 2003. Decreases in neurokinin-3 tachykinin receptor-immunoreactive and -mRNA levels are associated with salt appetite in the deoxycorticosterone-treated rat. Brain Research 960: 252-258.
Lucas L.R., Pompei P., and McEwen B.S. 2000. Salt appetite in salt-replete rats: Involvement of mesolimbic structures in deoxycorticosterone-induced salt craving behavior. Neuroendocrinology 71:386-395.
Lucas L.R., Angulo J.A., Le Moal M., McEwen B.S., Piazza P.V. 1998. Neurochemical characterization of individual vulnerability to addictive drugs in rats. European Journal of Neuroscience 10:3153-63.
Fig. Naïve rats exposed to a low-noise/ low light novel environment exhibit differences in individual locomotor responses to this type of novelty stress. Those animals displaying higher locomotor activity (high-responders: HRs) also show higher midbrain dopamine activity in addition to a higher propensity to self-administer psychostimulants and other drugs of abuse compared to lower activity rats (low-responders: LRs). In addition, it has been shown that the reactivity of stress hormones such as corticosterone (CORT) via the hypothalamic-pituitary-adrenal axis (HPA) is correlated with novelty-stress locomotor activity. Our data provide supportive evidence that circulating CORT levels interact with mesolimbic endogenous opiates such as enkephalin, resulting in individual rats that demonstrate greater vulnerablity to drug of abuse self-administration.
In the experiment shown here, the source of CORT (i.e., the adrenals) was removed surgically in 2 groups of animals. One group was adrenalectomized (ADX) and another was ADXed with stress hormone replacement (i.e., CORT). The Sham group serves as a control since it was operated but adrenals were left intact.
Rats were screened through the novelty stressor and categorized as LR or HR. Following this they were assigned to the Sham, ADX, or ADX+CORT groups. The top left figure shows a cumulative mean of locomotor activity (120 min.) where we no differences in locomotor activity among the 3 adrenalectomy groups pre-surgery can be seen. However, post-surgically, HRs showed greatest sensitivity to circulating levels of CORT (top, right). The bottom figure is a representational series of false-color photomicrographs of coronal sections through the regions of the rat brain associated with reward behavior. Here we see relative levels of [35S] -enkephalin-mRNA using in situ nucleic acid hybridization technology where red indicates high amounts of mRNA and we can see that enkephalin-mRNA levels were correlated to locomotor activity in HRs but not LRs. Thus, individual differences in endogenous opiates may be driving behavioral differences in drug abuse vulnerability in this important brain region.