Cocaine-induced anxiety: alleviation by diazepam, but not buspirone, dimenhydrinate or diphenhydramine.
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.
Paine
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TA
Department of Psychology, Queen's University, Kingston, Ontario, Canada.
Jackman
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Olmstead
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MC
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology; D002065:Buspirone / Q000494:pharmacology; D003042:Cocaine / Q000009:adverse effects*; D003220:Conflict, Psychological; D003975:Diazepam / Q000494:pharmacology*; D004111:Dimenhydrinate / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control* / Q000523:psychology
D014151:Anti-Anxiety Agents; D004155:Diphenhydramine; D003042:Cocaine; D004111:Dimenhydrinate; D003975:Diazepam; D002065:Buspirone