Prolonged treatment with haloperidol and clozapine in the rat: differential effects on spontaneous and theophylline-induced motor activity.
Difference in striatal dopamine D2 receptors and in spontaneous and theophylline-induced motor activity in rats withdrawn (for 72 h) from prolonged treatment with haloperidol or clozapine were studied. Haloperidol but not clozapine pretreatment increased the binding of the dopamine D2 antagonist [3H]raclopride in striatal membrane preparations, due to an increased number of striatal dopamine D2 receptors (Bmax) without changes in affinity (Kd). Haloperidol induced a significant increase (in motility and locomotion) and clozapine a decrease (in locomotion) of the spontaneous motor activity. Haloperidol but not clozapine pretreatment was associated with a stronger theophylline-induced motor activation. These results suggest that prolonged treatment with typical but not with atypical antipsychotics are associated with adaptive changes at both dopamine and adenosine receptors.
Ogren
S O
SO
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Ferré
S
S
Schwarcz
R
R
Fuxe
K
K
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D006220:Haloperidol / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2 / Q000502:physiology; D018047:Receptors, Purinergic P1 / Q000502:physiology; D013806:Theophylline
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D010726:Phosphodiesterase Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D018047:Receptors, Purinergic P1; D013806:Theophylline; D003024:Clozapine; D006220:Haloperidol