SINGER_Neurobiology_of_Learning_and_Memory_MAY_2022.pdf (898.71 kB)
Conditioned inhibition of amphetamine sensitization
journal contribution
posted on 2023-06-10, 03:38 authored by Anitra M Guillory, Stacy H Herrera, Lorinda K Baker, Nancy Bubula, Justin Forneris, Zhi-Bing You, Paul Vezina, Bryan SingerBryan SingerRepeated intermittent exposure to psychostimulants, such as amphetamine, leads to a progressive enhancement of the drug’s ability to increase both behavioral and brain neurochemical responses. The expression of these enhancements, known as sensitization, can be regulated by Pavlovian conditioned stimuli. Cues that are associated with drug experience can facilitate sensitization so that it only occurs in the presence of these stimuli (context-specific sensitization). In contrast, cues that are explicitly related to the absence of drugs (conditioned inhibitors) can prevent the expression of sensitization. We hypothesized that disrupting conditioned inhibition would enable amphetamine sensitization in new contexts. Using male Sprague Dawley rats and a two-context amphetamine conditioning procedure, we found that extinguishing amphetamine experience in one environment led to the loss of conditioned inhibition in a separate context. Thus, amphetamine-induced sensitized locomotion, as well as both enhanced dopamine and glutamate neurotransmission in the nucleus accumbens, were observed in a context where the drug was never experienced before. A similar loss of contextual control of sensitization was seen after using baclofen/muscimol microinjections to transiently inhibit the medial prefrontal cortex, basolateral amygdala, or ventral subiculum of the hippocampus. In other words, compared to control infusions, these intracranial injections of GABA-receptor agonists were able to block conditioned inhibitors from preventing the expression of sensitized locomotion. Together, these findings reveal the importance of conditioned inhibitors for regulating addiction-like behavior. The results suggest that dopaminergic and glutamatergic brain circuitry controls the context-specific expression of amphetamine sensitization.
History
Publication status
- Published
File Version
- Accepted version
Journal
Neurobiology of Learning and MemoryISSN
1074-7427Publisher
ElsevierExternal DOI
Volume
192Page range
1-10Article number
a107636Department affiliated with
- Psychology Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2022-05-24First Open Access (FOA) Date
2023-05-19First Compliant Deposit (FCD) Date
2022-05-23Usage metrics
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