Differential role of dopamine receptor subtypes in thermoregulation and stereotypic behavior in naive and reserpinized rats.
The present study explores the differential role of dopamine receptor subtypes and their interplay in the thermoregulation and stereotypic behavior in naive and acutely or chronically reserpinized rats. In naive rats, the D2 dopamine agonist B-HT920 (0.25-1 mg/kg) produced hypothermia, an effect sensitive to blockade by the D1/D2 antagonist haloperidol (0.5 mg/kg) and to potentiation by the D1 agonist SKF38393 (5 mg/kg). The hypothermic effect of the same doses of B-HT920 was reduced following acute reserpinization (5 mg/kg, 24 hr prior) but significantly enhanced following chronic reserpinization (1 mg/kg for 15 days), as compared with the B-HT920 effect in naive rats. Although SKF38393 (5 mg/kg) failed to elicit any significant effect on the rectal temperature, it potentiated the hypothermic effect of B-HT920 (0.25 mg/kg) in naive and acutely reserpinized rats. SKF38393 (5 mg/kg), on the contrary, produced a slight hyperthermia and failed to enhance the hypothermic effect of B-HT920 (0.25 mg/kg) following chronic reserpinization. A higher dose of SKF38393 (10 mg/kg), however, produced a significant rise in body temperature when administered alone or in combination with B-HT920 (0.25 mg/kg) in chronically reserpinized rats. Apomorphine (0.25-2 mg/kg), a mixed D1/D2 agonist, also produced a significant hypothermia in naive and acutely reserpinized rats. Following chronic reserpinization, however, apomorphine (0.25-1 mg/kg) produced a significant rise in body temperature, which was significantly enhanced upon co-administration with SKF38393 (5 mg/kg) but reversed to hypothermia when given in combination with B-HT920 (0.5 mg/kg). Similarly, B-HT920 (0.25-1 mg/kg) or apomorphine (0.25-2 mg/kg) produced a mild stereotypy in naive rats. The stereotypic effect of B-HT920 as well as of apomorphine was enhanced in parallel with the increase in the duration of reserpinization. SKF38393 (5 mg/kg) failed to elicit any significant stereotypic effect but significantly enhanced the stereotypic effect of B-HT920 (0.25 mg/kg) in naive or reserpinized rats. The above data, therefore, suggest a differential involvement of D2 and D1 receptors in temperature changes and stereotypy in naive and reserpinized rats, respectively.
Verma
A
A
Department of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
S K
SK
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D005260:Female; D008297:Male; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology*
D001381:Azepines; D015259:Dopamine Agents; D011954:Receptors, Dopamine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C024763:talipexole; D012110:Reserpine; D001058:Apomorphine