Rate of onset of dopamine transporter inhibitors assessed with intracranial self-stimulation and in vivo dopamine photometry in rats

• NCJ Number: 306228
• Journal: PSYCHOPHARMACOLOGY Volume: 240 Dated: 2023 Pages: 969–981
• Author(s): TYSON R. BAIRD; KIMBERLY N. KARIN,; SAMUEL A. MARSH; F. IVY CARROLL; J. M. L. MEDINA-CONTRERAS; S. STEVENS NEGUS; JOSE M. ELTIT
• Date Published: 2023
• Length: 13 pages
• Grant Number(s): 2019-R2-CX-0046
• Agencies: NIJ-Sponsored
• Publication Type: Research (Applied/Empirical)
• Award: The Effects of Synthetic Cathinone Chirality on Pharmacodynamics and Pharmacokinetics and Its Implications for Forensic Toxicology

Annotation

This study compared intracranial self-stimulation (ICSS) effects produced in rats by three DA transporter inhibitors that have different rates of onset (fastest to slowest: cocaine, WIN-35428, RTI-31) and that produced progressively weaker metrics of abuse potential in a drug self-administration procedure in rhesus monkeys. Additionally, in vivo photometry using the fluorescent DA sensor dLight1.1 targeted to the nucleus accumbens (NAc) was used to assess the time course of extracellular DA levels as a neurochemical correlate of behavioral effects.

Abstract

All three compounds produced ICSS facilitation and increased DA levels assessed by dLight. In both procedures, the rank order of onset rate was cocaine > WIN-35428 > RTI-31; however, in contrast to monkey drug self-administration results, maximum effects did not differ across compounds. These results provide additional evidence that drug-induced increases in DA drive ICSS facilitation in rats and illustrate the utility of both ICSS and photometry to evaluate the time course and magnitude of abuse-related drug effects in rats. (Published abstract provided)