PMID- 9192394
OWN - NLM
STAT- MEDLINE
DCOM- 19970812
LR  - 20191102
IS  - 1071-7323 (Print)
IS  - 1071-7323 (Linking)
VI  - 5
IP  - 3
DP  - 1997 May
TI  - Location and effect of obesity on putative anorectic binding sites in the rat 
      brain.
PG  - 201-7
AB  - Anorectic drugs such as mazindol bind to a class of low-affinity, 
      sodium-sensitive sites in the brain which are affected by ambient glucose 
      concentrations and a predisposition to develop diet-induced obesity (DIO). This 
      study used quantitative autoradiography of 10 nM 3H-mazindol binding to identify 
      the cellular location of these putative anorectic binding sites in the brain and 
      to assess the way in which the development of DIO affected their binding. We 
      previously showed that chow-fed, obesity-prone rats have widespread increases in 
      brain 3H-mazindol binding to these low-affinity sites as compared with 
      diet-resistant (DR) rats. Here, low-affinity 3H-mazindol binding was assessed in 
      the brains of eight rats which developed DIO vs. eight which were DR after three 
      months on a high-energy diet. DIO rats gained 89% more weight and had 117% higher 
      plasma insulin levels but no difference in plasma glucose levels compared with DR 
      rats. Along with these differences, low-affinity 3H-mazindol binding in DIO rats 
      was identical to that in DR rats in all of the 23 brain areas assessed. This 
      suggested that this binding was downregulated by the development of obesity in 
      DIO rats. In other chow-fed rats, stereotaxic injections of 
      5,7-dihydroxytryptamine and 6-hydroxydopamine (6OHDA) to ablate serotonin and 
      catecholamine nerve terminals in the ventromedial nucleus of the hypothalamus 
      (VMN) had no effect on 3H-mazindol binding. However, ibotenic acid injected into 
      the VMN, substantia nigra, pars reticulata, and pars compacta destroyed intrinsic 
      neurons and/or their local processes and decreased low-affinity 3H-mazindol 
      binding by 13%-22%. Destruction of dopamine neurons in the substantia nigra, pars 
      compacta, and noradrenergic neurons in the locus ceruleus with 6OHDA also reduced 
      3H-mazindol binding in those areas by 9% and 12%, respectively. This suggested 
      that up to 22% of putative anorectic binding sites may be located on the cell 
      bodies of dopamine, norepinephrine, and other neurons, but not on serotonin or 
      catecholamine nerve terminals in the brain. Binding to these sites may be 
      downregulated by the development of DIO, possibly as a result of the concomitant 
      hyperinsulinemia.
FAU - Dunn-Meynell, A A
AU  - Dunn-Meynell AA
AD  - Department of Neurosciences, NJ Medical School, Newark 07103, USA.
FAU - Levin, B E
AU  - Levin BE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Obes Res
JT  - Obesity research
JID - 9305691
RN  - 0 (Appetite Depressants)
RN  - C56709M5NH (Mazindol)
SB  - IM
MH  - Animals
MH  - Appetite Depressants/*metabolism
MH  - Autoradiography
MH  - Binding Sites
MH  - Brain/anatomy & histology/*metabolism
MH  - *Diet
MH  - Male
MH  - Mazindol/*metabolism
MH  - Obesity/etiology/*physiopathology
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 1997/05/01 00:00
MHDA- 1997/05/01 00:01
CRDT- 1997/05/01 00:00
PHST- 1997/05/01 00:00 [pubmed]
PHST- 1997/05/01 00:01 [medline]
PHST- 1997/05/01 00:00 [entrez]
AID - 10.1002/j.1550-8528.1997.tb00294.x [doi]
PST - ppublish
SO  - Obes Res. 1997 May;5(3):201-7. doi: 10.1002/j.1550-8528.1997.tb00294.x.