Aggressive and social behavior after alprazolam withdrawal: experimental therapy with Ro 19-8022.
The aim of the present study was to ascertain whether withdrawal from alprazolam can increase anxiety-like and aggressive behavior during intra species conflict in mice and, if so, whether a partial benzodiazepine agonist Ro 19-8022 is able to reverse these behavioral changes without untoward effects such as sedation. An experimental model consisting of interactions of pairs of singly-housed male mice with non-aggressive group-housed male mice was used. Alprazolam (1 mg/kg) was given orally twice daily for 8 days and once on the 9th day. When withdrawn from alprazolam (3 days after the last dose), mice reduced social investigation and increased the incidence of aggressive behavior in comparison to the pre-withdrawal level. However, the increase of aggression was moderate and occurred only in subjects with low pre-treatment levels of aggression. Ro 19-8022 (10 mg/kg) significantly antagonized the decrease of social behavior and the increase of aggression after alprazolam withdrawal without causing sedation or ataxia.
Krsiak
M
M
Department of Pharmacology, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic. miloslav.krsiak@lf3.cuni.cz
Podhorná
J
J
Miczek
K A
KA
D000374:Aggression / Q000187:drug effects*; D000525:Alprazolam / Q000009:adverse effects*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D004924:Escape Reaction / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D011187:Posture / Q000502:physiology; D011759:Pyrrolidines / Q000627:therapeutic use*; D011807:Quinolizines / Q000627:therapeutic use*; D012919:Social Behavior; D012931:Social Environment; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology*
D014151:Anti-Anxiety Agents; D011759:Pyrrolidines; D011807:Quinolizines; C076809:Ro 19-8022; D000525:Alprazolam