Cocaine-induced Anxiety: Alleviation by Diazepam, but Not Buspirone, Dimenhydrinate or Diphenhydramine

Behav Pharmacol. 2002 Nov;13(7):511-23. doi: 10.1097/00008877-200211000-00001.


Clinical reports and animal experiments indicate that both cocaine administration and cocaine withdrawal increase anxiety. We investigated the ability of a number of putative anxiolytic agents to alleviate these anxiety states using the elevated plus-maze. Rats in the cocaine condition received either saline or cocaine (20 mg/kg) 40 min prior to testing; those in the withdrawal condition were tested 48 h following a chronic treatment regime (saline or cocaine 20 mg/kg per day for 14 days). Prior to testing, animals received a benzodiazepine (1.0 or 2.0 mg/kg diazepam), a serotonergic agonist (0.5 or 1.0 mg/kg buspirone), an antihistamine (50 mg/kg dimenhydrinate or 27 mg/kg diphenhydramine) or a saline injection. All drugs were administered intraperitoneally. Cocaine administration and cocaine withdrawal reduced the percentage time spent on and the number of entries into the open arms. Diazepam dose-dependently alleviated cocaine withdrawal-induced anxiety and non-significantly attenuated cocaine-induced anxiety. Buspirone, dimenhydrinate and diphenhydramine did not consistently alleviate the anxiety caused by either cocaine pre-treatment regime; in the saline conditions, however, each of these treatments was anxiogenic. In summary, benzodiazepines alleviated cocaine-induced anxiety, while future research on the ability of serotonergic and antihistaminergic drugs to alleviate these anxiety states is warranted.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Anxiety / chemically induced
  • Anxiety / prevention & control*
  • Anxiety / psychology
  • Buspirone / pharmacology
  • Cocaine / adverse effects*
  • Conflict, Psychological
  • Diazepam / pharmacology*
  • Dimenhydrinate / pharmacology
  • Diphenhydramine / pharmacology
  • Dose-Response Relationship, Drug
  • Exploratory Behavior / drug effects
  • Injections, Intraperitoneal
  • Male
  • Maze Learning / drug effects
  • Rats
  • Rats, Long-Evans
  • Substance Withdrawal Syndrome / prevention & control*
  • Substance Withdrawal Syndrome / psychology


  • Anti-Anxiety Agents
  • Diphenhydramine
  • Cocaine
  • Dimenhydrinate
  • Diazepam
  • Buspirone