Evidence for the involvement of dopamine D(1) and D(2) receptors in mediating the decrease of food intake during repeated treatment with amphetamine.
Repeated treatment with amphetamine (AMPH), a well-known anorectic agent, into animals could induce anorexia on day 1 and produce a gradual reversion of food intake (tolerant anorexia) on the following days. It is unknown whether these feeding changes are related to dopamine (DA) and/or noradrenergic neurotransmission. Thus, the present study investigated the subtype of receptor mediating AMPH-induced anorexia. Daily food intake was measured after various drugs were given. Pretreatment with haloperidol, an antagonist of DA receptors, may lead to inhibition of AMPH-induced anorexia. However, pretreatment with the alpha-adrenoceptor antagonist phentolamine, and the beta-adrenoceptor antagonist propranolol, failed to modify the action of AMPH, suggesting the involvement of DA receptors but not adrenoceptors in the action of AMPH-induced anorexia. Furthermore, pretreatment with SCH 23390 at a dose sufficient to block D(1) receptors or pimozide at a dose sufficient to inhibit D(2) receptors blocked AMPH-induced anorexia, indicating the involvement of D(1) and D(2) receptors. In a study of tolerant anorexia, repeated treatment with the D(1)/D(2) agonist apomorphine, but not the D(1) agonist SKF 38393 or D(2) agonist quinpirole, induced an AMPH-like tolerant feeding response, providing evidence for conjoint action of D(1) and D(2) receptors in the effect. The present results suggest that both D(1) and D(2) receptors are involved in anorexia and tolerant anorexia induced by chronic intermittent administration of AMPH.
Chen
T Y
TY
Department of Internal Medicine, Chung-Shan Medical and Dental College, Taichung, Taiwan, ROC.
Duh
S L
SL
Huang
C C
CC
Lin
T B
TB
Kuo
D Y
DY
D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000855:Anorexia / Q000139:chemically induced; D001067:Appetite Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D001069:Appetite Regulation / Q000187:drug effects*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D004338:Drug Combinations; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*
D001067:Appetite Depressants; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004338:Drug Combinations; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000661:Amphetamine