Previous exposure to VTA amphetamine enhances cocaine self-administration under a progressive ratio schedule in a D1 dopamine receptor dependent manner

Neuropsychopharmacology. 2002 Dec;27(6):970-9. doi: 10.1016/S0893-133X(02)00379-2.


The effect of previous exposure to amphetamine (AMPH) in the ventral tegmental area (VTA) on the subsequent self-administration of cocaine was assessed. Rats in different groups were pre-exposed to three injections into the VTA of either saline (0.5 microl/side) or AMPH (2.5 microg/0.5 microl/side). Injections were given once every third day. Starting 7-10 days after the last pre-exposure injection, rats were trained to self-administer cocaine (0.3 mg/kg/infusion) under fixed ratio 1 and 2 (FR1 and FR2) schedules and then tested under a progressive ratio (PR) schedule of reinforcement for six consecutive days. No differences between groups were observed during self-administration training under the FR schedules of reinforcement. However, when tested under the PR schedule, VTA AMPH pre-exposed rats worked more and, as a result, obtained more infusions of cocaine than saline pre-exposed rats. Rats in a separate group pre-exposed to VTA AMPH but co-infused with the D(1)-like dopamine (DA) receptor antagonist SCH23390 (0.25 microg/0.5 microl/side) did not show enhanced cocaine self-administration. These rats, as well as others pre-exposed to VTA SCH23390 alone showed levels of cocaine self-administration similar to saline pre-exposed rats. Thus, in a manner paralleling the sensitization of AMPH-induced locomotion and nucleus accumbens DA overflow, previous exposure to AMPH in the VTA leads to enhanced intravenous self-administration of cocaine and activation of D(1) DA receptors in this site during pre-exposure is necessary for the production of this effect.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amphetamine / pharmacology*
  • Animals
  • Cocaine / pharmacology*
  • Drug Synergism
  • Male
  • Rats
  • Rats, Long-Evans
  • Receptors, Dopamine D1 / physiology*
  • Reinforcement Schedule*
  • Self Administration / psychology
  • Ventral Tegmental Area / drug effects*
  • Ventral Tegmental Area / physiology


  • Receptors, Dopamine D1
  • Amphetamine
  • Cocaine