Article

Simultaneous dopamine and single-unit recordings reveal accumbens GABAergic responses: implications for intracranial self-stimulation.

Department of Chemistry and Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 01/2006; 102(52):19150-5. DOI: 10.1073/pnas.0509607102
Source: PubMed

ABSTRACT Intracranial self-stimulation (ICS) is a motivated behavior that results from contingent activation of the brain reward system. ICS with stimulating electrodes placed in the medial forebrain bundle (MFB) is particularly robust. However, the neurons that course through this pathway use a variety of neurotransmitters including dopamine and GABA. For this reason, the neurotransmitters that are central to this behavior, and the specific roles that they subserve, remain unclear. Here, we used extracellular electrophysiology and cyclic voltammetry at the same electrode in awake rats to simultaneously examine cell firing and dopamine release in the nucleus accumbens (NAc) during ICS and noncontingent stimulation of the MFB. ICS elicited dopamine release in the NAc and produced coincident time-locked changes (predominantly inhibitions) in the activity of a subset of NAc neurons. Similar responses were elicited with noncontingent stimulations. The changes in firing rate induced by noncontingent stimulations were reversed by the GABA(A) receptor antagonist bicuculline. Most time-locked unit activity was unaffected by D1 or D2-like dopamine-receptor antagonists, or by inhibition of evoked dopamine release, although, for a minority of units, the D1 dopamine-receptor antagonist SCH23390 attenuated neural activity. Thus, neurons in the NAc are preferentially inhibited by GABA(A) receptors after MFB stimulation, a mechanism that may also be important in ICS.

0 Followers
 · 
59 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Reinforcement-based learning models predict that the strength of association between cues and outcomes is driven by aspects of outcome value. However, animals routinely make associations between contingent stimuli in the world, even if those associations hold no value to the organism. At the neural level, the nucleus accumbens (NAc) is known to encode associative information, but it is not known whether this encoding is specific for value-based information (consistent with reinforcement-based models) or if the NAc additionally plays a more general role in forming predictive associations, independent of outcome value. To test this, we employed a sensory preconditioning (SPC) task where rats initially (Preconditioning) received either contingent pairings of 2 neutral stimuli (e.g., tone [A] and light [X]; "Paired"), or random noncontingent presentations ("Unpaired"). After cue X was subsequently conditioned with food (First-Order Conditioning), the effect of preconditioning was assessed in Phase 3 (Test) by presentations of cue A alone. Electrophysiological recordings from the NAc core showed significant increases in phasic encoding for the stimuli in the Paired (but not Unpaired) condition as well as during test. Further, these effects were only seen in Paired rats that showed successful behavior during test (Good Learners), but not those who did not (Poor Learners) or Unpaired controls. These findings reveal a role for the NAc in the encoding of associative contingencies independent of value, and suggest that this structure also plays a more general role in forming associations necessary for predictive behavior. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
    Behavioral Neuroscience 10/2014; 128(5):567-578. DOI:10.1037/a0037797 · 3.25 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionAlcohol-associated cues activate both ventral and dorsal striatum in functional brain imaging studies of heavy drinkers. In rodents, alcohol-associated cues induce changes in neuronal firing frequencies and increase dopamine release in ventral striatum, but the impact of alcohol-associated cues on neuronal activity in dorsal striatum is unclear. We previously reported phasic changes in action potential frequency in the dorsomedial and dorsolateral striatum after cues that signaled alcohol availability, prompting approach behavior.Methods We investigated the hypothesis that dopamine transmission modulates these phasic firing changes. Rats were trained to self-administer alcohol, and neuronal activity was monitored with extracellular electrophysiology during “anticipatory” cues that signaled the start of the operant session. Sessions were preceded by systemic administration of the D1-type dopamine receptor antagonist SCH23390 (0, 10, and 20 μg/kg).ResultsSCH23390 significantly decreased firing rates during the 60 s prior to cue onset without reducing phasic excitations immediately following the cues. While neuronal activation to cues might be expected to initiate behavioral responses, in this study alcohol seeking was reduced despite the presence of dorsal striatal excitations to alcohol cues.Conclusions These data suggest that D1 receptor antagonism reduces basal firing rates in the dorsal striatum and modulates the ability of neuronal activation to “anticipatory” cues to initiate alcohol seeking in rats with an extensive history of alcohol self-administration.
    12/2014; 5(2). DOI:10.1002/brb3.305
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The role of serotonin in depression and antidepressant treatment remains unresolved despite decades of research. In this paper, we make three major claims. First, serotonin transmission is elevated in multiple depressive phenotypes, including melancholia, a subtype associated with sustained cognition. The primary challenge to this first claim is that the direct pharmacological effect of most symptom-reducing medications, such as the selective serotonin reuptake inhibitors (SSRIs), is to increase synaptic serotonin. The second claim, which is crucial to resolving this paradox, is that the serotonergic system evolved to regulate energy. By increasing extracellular serotonin, SSRIs disrupt energy homeostasis and often worsen symptoms during acute treatment. Our third claim is that symptom reduction is not achieved by the direct pharmacological properties of SSRIs, but by the brain's compensatory responses that attempt to restore energy homeostasis. These responses take several weeks to develop, which explains why SSRIs have a therapeutic delay. We demonstrate the utility of our claims by examining what happens in animal models of melancholia and during acute and chronic SSRI treatment.
    Neuroscience & Biobehavioral Reviews 02/2015; 51:164-188. DOI:10.1016/j.neubiorev.2015.01.018 · 10.28 Impact Factor

Preview

Download
0 Downloads
Available from