Catecholamines in the bed nucleus of the stria terminalis reciprocally respond to reward and aversion

Abstract

Background: Traditionally, norepinephrine has been associated with stress responses, whereas dopamine has been associated with reward. Both of these catecholamines are found within the bed nucleus of the stria terminalis (BNST), a brain relay nucleus in the extended amygdala between cortical/limbic centers, and the hypothalamic-pituitary-adrenal axis. Despite this colocalization, little is known about subsecond catecholamine signaling in subregions of the BNST in response to salient stimuli.

Methods: Changes in extracellular catecholamine concentration in subregions of the BNST in response to salient stimuli were measured within the rat BNST with fast-scan cyclic voltammetry at carbon-fiber microelectrodes.

Results: A discrete subregional distribution of release events was observed for different catecholamines in this nucleus. In addition, rewarding and aversive tastants evoked inverse patterns of norepinephrine and dopamine release in the BNST. An aversive stimulus, quinine, activated noradrenergic signaling but inhibited dopaminergic signaling, whereas a palatable stimulus, sucrose, inhibited norepinephrine while causing dopamine release.

Conclusions: This reciprocal relationship, coupled with their different time courses, can provide integration of opposing hedonic states to influence response outputs appropriate for survival.

Figure 1

Electrically evoked catecholamine responses in the vBNST and dlBNST. (A) and (B) (left) Diagram of the region examined at 0.0 mm from bregma(24). The dotted lines illustrate the approximate path of the carbon-fiber microelectrode through the vBNST and dlBNST. (A) and (B)(right) Evoked (60 Hz, 40 pulses, 150 µA) catecholamine concentrations recorded at the depth indicated. The red bars under the current trace show the electrical stimulation time. Inset: background-subtracted cyclic voltammogram measured during the indicated trace. Abbreviations: CPu, caudate-putamen; AC, anterior commissure; dmBNST, dorsomedial bed nucleus of the stria terminalis; VP, ventral pallidum; LV, lateral ventricle.

Figure 2

Dopamine signaling in the dlBNST in response to palatable and aversive tastants. (A) Intra-oral infusions of sucrose increase dopamine release. The upper trace is the average dopamine concentration change over 15 trials in response to intraoral sucrose infusions in a single animal (infusions during the red bar). The color plot shows the averaged cyclic voltammograms collected during the 15 trials. Catecholamine concentration changes are apparent in the color plots at the potential for its oxidation (~ +0.65 V, dotted white line) and its reduction (~ −0.2 V, solid white line). (B) Trial-by-trial changes of dopamine concentration from the animal shown in (A) in response to intra-oral sucrose infusion. (C) Upper trace is the average dopamine concentration change over 15 trials in response to intra-oral infusions of quinine in a single animal (infusions during the red bar). The color plot shows the average of all of the cyclic voltammograms collected during the 15 trials in this animal. (D) Trial-by-trial changes of dopamine concentration from the animal shown in (C) in response to intraoral infusions of quinine. In (A) and (C) the mean is given by the solid lines and ± s.e.m. is given by the dotted lines.

Figure 3

Average concentration change and time course for dopamine in the dlBNST. (A) Maximal dopamine concentration change measured in response to infused tastants (P < 0.005 for sucrose, P < 0.01 for quinine). (B) Time for dopamine to change by 20 nM (t_±20nM) after initiation of tastant infusion. (C, D) Effect of idazoxan (IDA, 5 mg/kg), desipramine (DMI, 15 mg/kg), raclopride (RA, 2 mg/kg) and GBR 12909 (GBR, 15 mg/kg) on electrically evoked dopamine release. (C) Maximal dopamine concentration ([DA]) and (D) time to clear the released dopamine to half of its maximal concentration (t_1/2). * Indicates significantly different from control values (P < 0.05).

Figure 4

Norepinephrine signaling in the vBNST in response to palatable and aversive tastants in a single animal. (A) Intra-oral infusions of sucrose decrease norepinephrine release. The upper trace is the average norepinephrine concentration change over 15 trials in response to intra-oral sucrose infusions in a single animal (infusions during the red bar). The color plot shows the averaged cyclic voltammograms collected during the 15 trials. White lines are as in Figure 2(A). (B) Trial-by-trial changes of norepinephrine concentration from the animal shown in (A) in response to intra-oral sucrose infusion. (C) Upper trace is the average norepinephrine concentration change over 15 trials in response to intra-oral infusions of quinine in a single animal (infusions during the red bar). The color plot shows the average of all of the cyclic voltammograms collected during the 15 trials in this animal. (D) Trial-by-trial changes of norepinephrine concentration from the animal shown in (C) in response to intra-oral infusions of quinine. In (A) and (C) the mean is given by the solid lines and ± s.e.m. is given by the dotted lines.

Figure 5

Average concentration change and time course for norepinephrine in the vBNST. (A) Maximal norepinephrine concentration change measured in response to infused tastants (p < 0.0001 for sucrose, P < 0.0001 for quinine). (B) Time for 20 nM norepinephrine changes to occur (t_±20nM) after initiation of tastant infusion. (C, D) Effect of idazoxan (IDA, 5 mg/kg), desipramine (DMI, 15 mg/kg), raclopride (RA, 2 mg/kg) and GBR 12909 (GBR, 15 mg/kg) on electrically evoked norepinephrine release. (C) Maximal evoked norepinephrine concentration ([NE]). (D) half-decay time (t_1/2). * Indicates significantly different from control values (P < 0.05).

Figure 6

Catecholamine signaling at a single location in the border of the dl- and dmBMST. (A) The upper trace is the average catecholamine concentration change over 15 trials in response to intra-oral sucrose infusions in a single animal (infusions during the red bar). The color plot shows the averaged cyclic voltammograms collected during the 15 trials. (B) Trial-by-trial changes of catecholamine concentration from the animal shown in (A) in response to intra-oral sucrose infusion. (C) Upper trace is the average catecholamine concentration change over 15 trials in response to intra-oral infusions of quinine in a single animal (infusions during the red bar). The color plot shows the average of all of the cyclic voltammograms collected during the 15 trials in this animal. (D) Trial-by-trial changes of dopamine concentration from the animal shown in (C) in response to intra-oral infusions of quinine. In (A) and (C) the mean is given by the solid lines and ± s.e.m. is given by the dotted lines. (E) Responses in this location to electrical stimulation before and after administration of the RA, (predrug [CA] = 167 ± 7 nM, 20 min post RA [CA] = 236 ± 5 nM P < 0.005, 3 trials) and IDA ([CA] = 257 ± 7 nM 50 min after RA, 20 min after IDA [CA] = 414 ± 4 nM, P < 0.0001, 3 trials). (F) Average concentration traces (mean ± s.e.m. denoted by solid and broken lines, respectively) following intra-oral sucrose (upper, n = 18 infusions) and quinine (lower, n = 14 infusions) after administration of RA and IDA. (G) An electrolytic lesion (denoted by broken red circle) in the BNST at the site where these recordings were made. Abbreviations: CPu, caudate-putamen; AC, anterior commissure; VP, ventral pallidum; LV, lateral ventricle; dm, dorsomedial bed nucleus of the stria terminalis; dl, dorsolateral bed nucleus of the stria terminalis.