Antiadrenergic Agents Infused into the Central Amygdala Attenuate Brain Reward Deficits during Acute Opioid Withdrawal in Rats
Year: 2014
Type: dissertation
Abstract: Drug addiction is a chronic relapsing disorder characterized by withdrawal, loss of control and high rates of relapse. Avoidance of the aversive consequences of withdrawal can progressively become an increasingly important motivating factor for addicted individuals to continue their destructive habit. The motivational consequences of withdrawal may begin after a single, acute, dose of an addictive drug, which causes rapid neuroadaptiation in brain stress circuitry (Schulteis 2010). Of particular interest in the study of withdrawal are the stress neurotransmitters Norepinephrine (NE) and Corticotrophin Releasing Factor (CRF). The present study examined the neuro-adaptive changes in NE signaling that follow a single bout of morphine intoxication in rats. Using the intracranial self-stimulation (ICSS) paradigm to measure brain stimulation reward (BSR) thresholds, the role of NE in the central amygdala (CeA) was examined during acute withdrawal. Antagonism of [alpha]1 adrenoreceptors in the CeA with prazosin dose- dependently attenuated the depression-like increases in BSR thresholds produced by precipitated acute morphine withdrawal with the opioid antagonist naloxone. Reduction in NE release with the [alpha]2 autoreceptor agonist UK 14,304 did not significantly decrease thresholds. NE activity in the amygdala, in conjunction with CRF, may contribute in part to the dysphoria-like state of opioid withdrawal. These results provide further evidence for a CRF/NE feed-forward mechanism which might amplify stress responses in the development of opioid dependence. Pharmacological manipulation of NE and CRF systems can potentially lead to therapeutic treatment of opioid addiction through reducing the aversive affective states produced by withdrawal- induced hyperactivity of these stress systems
Author: Ravi Wettasinghe
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2490075982