Haloperidol and risperidone have specific effects on altered pain sensitivity in the ketamine model of schizophrenia.
BACKGROUND
The ketamine (ket) model reflects features of schizophrenia as well as secondary symptoms such as altered pain sensitivity.


OBJECTIVE
In the present study, we investigated the effect of subchronic oral treatment with haloperidol (hal, 0.075 mg/kg) and risperidone (ris, 0.2 mg/kg) on altered pain perception and locomotor activity in this model.


RESULTS
In reaction to 5 mg/kg morphine, ket pretreated animals showed a diminished analgesic response. Hal had no analgesic effect per se, but the compound normalised the analgesic reaction to morphine in the ket pretreated animals. The effect of ris was complex. First, there was no analgesic effect per se, and control animals showed a dose-dependent increase in the analgesic index after morphine injection. In the ket group treated with ris, the analgesic response to 5 mg/kg morphine was attenuated and in response to 10 mg/kg analgesia was comparable with that measured in controls. The reduced analgesic effect was not due to pharmacokinetic differences in morphine metabolism. After administration via drinking water in saline-injected control animals, the hal blood serum concentration was 2.6 +/- 0.45 ng/ml. In ket-injected animals, the mean serum concentration of hal amounted to 1.2 +/- 0.44 ng/ml. In the experiment using ris, animals in the control group had higher ris serum concentrations compared with ket-injected animals. In control animals, morphine dose dependently decreased locomotor activity. This effect was significantly stronger in the ket pretreated groups.


CONCLUSIONS
Hal and ris had different effects on altered pain sensitivity. It was hypothesised that these results are connected with alterations in dopamine D2 and mu opioid receptor binding.
Becker
Axel
A
Faculty of Medicine, Institute of Pharmacology and Toxicology, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany. axel.becker@med.ovgu.de
Grecksch
Gisela
G
Zernig
Gerald
G
Ladstaetter
Elisabeth
E
Hiemke
Christoph
C
Schmitt
Ulrich
U
D000701:Analgesics, Opioid / Q000097:blood / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists; D006220:Haloperidol / Q000097:blood / Q000494:pharmacology*; D007649:Ketamine; D008297:Male; D009020:Morphine / Q000097:blood / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000523:psychology*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000097:blood / Q000494:pharmacology*; D012559:Schizophrenia / Q000139:chemically induced*; D012565:Schizophrenic Psychology
D000701:Analgesics, Opioid; D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D009020:Morphine; D006220:Haloperidol; D018967:Risperidone