Repeated stimulation of L-type calcium channels in the rat ventral tegmental area mimics the initiation of behavioral sensitization to cocaine

Psychopharmacology (Berl). 2000 Sep;152(1):110-8. doi: 10.1007/s002130000518.

Abstract

Rationale: A substantial body of evidence indicates that ion flux through L-type calcium channels and N-methyl-D-aspartate (NMDA) receptors contributes to behavioral sensitization to cocaine.

Objectives: The following experiments were designed to evaluate the role of calcium influx through L-type calcium channels or NMDA receptors in the ventral tegmental area (VTA) in the initiation of behavioral sensitization to cocaine.

Methods: The L-type calcium channel agonist BayK 8644, the glutamate agonist NMDA, or vehicle was microinjected into the VTA on 3 consecutive days. Following a 2-week withdrawal period, all rats received a challenge injection of cocaine (15 mg/kg, i.p.) in order to assess potential cross-sensitization with the NMDA or BayK 8644 pretreatments.

Results: Repeated intra-VTA microinjections of BayK 8644, but not NMDA, resulted in an augmentation of the behavioral response to cocaine.

Conclusions: These results indicate that calcium influx through L-type calcium channels produces neurophysiological adaptations that mimic those resulting from intermittent exposure to cocaine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Animals
  • Behavior, Animal / drug effects*
  • Calcium Channel Agonists / pharmacology*
  • Calcium Channels, L-Type / drug effects*
  • Cocaine / pharmacology*
  • Dopamine Uptake Inhibitors / pharmacology*
  • Male
  • Microinjections
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / agonists
  • Stereotyped Behavior / drug effects
  • Ventral Tegmental Area / physiology*

Substances

  • Calcium Channel Agonists
  • Calcium Channels, L-Type
  • Dopamine Uptake Inhibitors
  • Receptors, N-Methyl-D-Aspartate
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Cocaine