Research reportPlace preferences induced by electrical stimulation of the external lateral parabrachial subnucleus in a sequential learning task: Place preferences induced by NLPBe stimulation
Introduction
The parabrachial complex has been associated with various rewarding behavioral processes, including those related to nutrient intake [[1], [2], [3], [4]]. Several rewarding processes have been related to the external lateral parabrachial nucleus (NLPBe), which is activated after the administration of rewarding nutrients such as glucose, lactose, or sucrose [[1], [2], [3]] or of drugs of abuse [[5], [6], [7], [8]].
Electrical stimulation of the NLPBe can induce taste preferences for associated flavors [9] and can generate place preferences in concurrent learning tasks [[10], [11], [12], [13]]. In these studies, place preferences were induced using a concurrent procedure, in which the animals could move freely in the maze and intracranial electrical stimulation was associated with their voluntary stay in one of the two maze compartments. It has been observed that place preferences induced by NLPBe stimulation by means of this procedure are blocked by naloxone administration [9,13], reflecting the high density of opioid receptors in this region [6,8,[14], [15], [16]]. Interestingly, preferences induced by stimulating the lateral hypothalamus are not inhibited by naloxone administration [17]. Furthermore, it has not yet been established whether electrical stimulation of the NLPBe can sustain self-stimulation behaviors [9].
Dopaminergic antagonists, specifically tiapride, do not block place preferences induced by NLPBe electrical stimulation [18]. It has been observed that electrical intracranial self-stimulation (ICSS) of the lateral hypothalamus can be affected by the administration of antipsychotics such as pimozide [19].
Repeated NLPBe stimulation produces tolerance to its rewarding effects, evidenced by a progressive loss of the capacity of stimulation to generate place preferences when repeatedly applied [20], again recalling the effect of drugs of abuse [[21], [22], [23]].
It has also been proposed that the key factor in developing tolerance to the rewarding effects of NLPBe stimulation is that its administration is not contingent on the behavior of the animal, unlike stimulation of the lateral hypothalamus, which does not produce tolerance regardless of its contingent (concurrent) or sequential administration [24].
All of the above findings have led to the proposal of a potential axis related to brain reward that includes the NLPBe and appears to differ from the axis that includes the lateral hypothalamus.
However, it has not been demonstrated that the electrical stimulation of these regions can generate place preference learning in non-contingent (sequential) tasks, in which animals are confined while receiving intracranial electrical stimulation and then undergo a choice test without stimulation in a later phase (as in the above studies). In this way, the sequential procedure involves an acquisition phase with the simultaneous presentation of rewarding stimulus and associated maze compartment, followed by a delay before the learning of the animal is tested.
It is well documented that the sequential procedure can be used to establish place preferences induced by the administration of natural rewards and especially drugs of abuse [[25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37]]. Thus, it has been widely reported that place preference conditioning is a highly sensitive tool to measure the rewarding properties of morphine [29,31,33,[38], [39], [40], [41], [42], [43], [44]].
However, rewarding electrical stimulation of the NLPBe shares some characteristics with this type of associated reward (e.g., from drugs of abuse) but differs from the reward produced by LH stimulation (see above), which can be blocked by the administration of naloxone [9,13] but not tiapride [18]. It is also possible to develop tolerance towards the rewarding properties of NLPBe stimulation when its administration is repeated [20] or not contingent on the behavior of the animal [24]. These differentiating characteristics of PNLBe stimulation-induced reward have only been tested using concurrent procedures, and it has yet to be demonstrated that this stimulation can sustain sequential place learning.
With this background, the objective of this study was to explore the possibility of inducing place preferences or aversions by electrical stimulation of the NLPBe in a sequential task. This parabrachial region was previously related to concurrent taste learning alone [45,46] but is now associated with learning tasks in which the stimulation is not contingent on the behavior of the animal in the test phase.
Section snippets
Subjects and surgical procedure
Thirty-three male Wistar rats from the breeding colony at the University of Granada, weighing 280−350 g at baseline, were used in this study. Animals were housed in methacrylate cages with water and food ad libitum (A-04, Panlab Diets S.L., Barcelona, Spain). The laboratory was maintained at 20−24 °C with a 12:12 h light/dark cycle. All experimental procedures were conducted during light periods with white noise.
The animals remained under these conditions for an adaptation period of at least
Results
Given that analysis of sequential procedure results (Part One) took account of the concurrent procedure results (Part Two), the latter are reported first Table 2.
Discussion
The results of this study demonstrate that place preference behaviors can be induced by electrical stimulation of the NLPBe, using a sequential procedure that involves confinement of the animals while receiving the stimulation. However, the same was not observed for place aversion induced by NLPBe stimulation, which can be achieved using concurrent but not sequential procedures, at least when the duration of electrical stimulation is the same.
The concurrent procedure yielded three types of
Author statement
The authors do not have permission to share data
Acknowledgements
The authors are grateful to Richard and Layla Davies for assistance with the English version of this paper. This research was supported in part by the University of Granada and Spanish Ministry of Education and Culture (National R + D Plan PB98-1284; SEJ2007-61839/PSIC & PSI2010-17400).
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