phMRI, neurochemical and behavioral responses to psychostimulants distinguishing genetically selected alcohol-preferring from genetically heterogenous rats

Addict Biol. 2019 Sep;24(5):981-993. doi: 10.1111/adb.12671. Epub 2018 Oct 17.

Abstract

Alcoholism is often associated with other forms of drug abuse, suggesting that innate predisposing factors may confer vulnerability to addiction to diverse substances. However, the neurobiological bases of these factors remain unknown. Here, we have used a combination of imaging, neurochemistry and behavioral techniques to investigate responses to the psychostimulant amphetamine in Marchigian Sardinian (msP) alcohol-preferring rats, a model of vulnerability to alcoholism. Specifically, we employed pharmacological magnetic resonance imaging to investigate the neural circuits engaged by amphetamine challenge, and to relate functional reactivity to neurochemical and behavioral responses. Moreover, we studied self-administration of cocaine in the msP rats. We found stronger functional responses in the extended amygdala, alongside with increased release of dopamine in the nucleus accumbens shell and augmented vertical locomotor activity compared with controls. Wistar and msP rats did not differ in operant cocaine self-administration under short access (2 hours) conditions, but msP rats exhibited a higher propensity to escalate drug intake following long access (6 hours). Our findings suggest that neurobiological and genetic mechanisms that convey vulnerability to excessive alcohol drinking also facilitate the transition from psychostimulants use to abuse.

Keywords: addiction; phMRI; reward.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcoholism / diagnostic imaging*
  • Alcoholism / metabolism
  • Amphetamine / pharmacology*
  • Amygdala / diagnostic imaging
  • Amygdala / drug effects
  • Amygdala / metabolism
  • Animals
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / metabolism
  • Central Nervous System Stimulants / pharmacology*
  • Cocaine / administration & dosage*
  • Conditioning, Operant
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Functional Neuroimaging
  • Glutamic Acid / drug effects
  • Glutamic Acid / metabolism
  • Locomotion
  • Magnetic Resonance Imaging
  • Microdialysis
  • Nucleus Accumbens / diagnostic imaging
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Rats
  • Self Administration
  • gamma-Aminobutyric Acid / drug effects
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Central Nervous System Stimulants
  • Dopamine Uptake Inhibitors
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Amphetamine
  • Cocaine
  • Dopamine