PMID- 9748090
OWN - NLM
STAT- MEDLINE
DCOM- 19981209
LR  - 20190712
IS  - 0031-9384 (Print)
IS  - 0031-9384 (Linking)
VI  - 64
IP  - 3
DP  - 1998 Jun 1
TI  - A search for the metabolic signal that sensitizes lateral hypothalamic 
      self-stimulation in food-restricted rats.
PG  - 251-60
AB  - Food deprivation and restriction increase the rewarding potency of food, drugs of 
      abuse, and electrical brain stimulation. Based on evidence that the rewarding 
      effects of these stimuli are mediated by the same neuronal circuitry, lateral 
      hypothalamic self-stimulation (LHSS) was used to investigate the involvement of 
      various metabolic signals in the sensitization of reward. In Experiment 1, 
      glucoprivation with 2-deoxy-d-glucose (150 mg/kg, intraperitoneally (i.p.)) and 
      lipoprivation with nicotinic acid (150 mg/kg, subcutaneously (s.c.)), 
      individually and in combination, failed to affect the LHSS threshold in ad 
      lib.-fed rats. These results suggest that signals associated with acute shortage 
      of metabolic substrate do not sensitize reward. Because numerous responses to 
      more prolonged negative energy balance are mediated by neuropeptide Y (NPY), the 
      effect of exogenous neuropeptide Y upon LHSS was investigated in Experiment 2. 
      Intraventricular infusion of orexigenic neuropeptide Y doses (2.0, 5.0, and 12.5 
      g), in ad lib.-fed rats, had no effect on LHSS threshold. In Experiment 3, other 
      concomitants of prolonged negative energy balance--high circulating levels of 
      free fatty acids (FFA) and beta-hydroxybutyrate (HDB)-were investigated. 
      Nicotinic acid (250 mg/kg, s.c.), which suppressed serum HDB and FFA levels, had 
      no effect on LHSS in food-restricted or ad lib.-fed rats. Mercaptoacetate (68.4 
      mg/kg, i.p.), which suppressed serum HDB levels and exacerbated the elevation of 
      FFA levels, also had no effect. Thus, the brain reward system, if modulated by 
      these substances, is not affected by transient, though marked, changes in their 
      levels. To investigate the effect of a sustained increase in levels of FFA and 
      HDB, a "ketogenic" diet was employed. Although this diet produced a fourfold 
      increase in serum HDB levels, it had no effect on LHSS thresholds. Moreover, the 
      failure of mercaptoacetate (68.4 mg/kg, i.p.) to decrease LHSS thresholds in 
      these rats supports the conclusion that acute shortage of metabolic substrate 
      does not sensitize reward. Other possible mechanisms of reward sensitization, 
      including sustained decreases in circulating insulin and leptin and increases in 
      corticosterone, are discussed.
FAU - Cabeza De Vaca, S
AU  - Cabeza De Vaca S
AD  - Department of Psychiatry, New York University Medical Center, NY 10016, USA.
FAU - Holiman, S
AU  - Holiman S
FAU - Carr, K D
AU  - Carr KD
LA  - eng
GR  - DA-00292/DA/NIDA NIH HHS/United States
GR  - DA-03956/DA/NIDA NIH HHS/United States
GR  - T32 DA-07254/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Physiol Behav
JT  - Physiology & behavior
JID - 0151504
RN  - 0 (Antimetabolites)
RN  - 0 (Appetite Stimulants)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Ketone Bodies)
RN  - 0 (Neuropeptide Y)
RN  - 2679MF687A (Niacin)
RN  - 9G2MP84A8W (Deoxyglucose)
SB  - IM
MH  - Animals
MH  - Antimetabolites/pharmacology
MH  - Appetite Stimulants/administration & dosage/pharmacology
MH  - Deoxyglucose/pharmacology
MH  - Diet
MH  - Electric Stimulation
MH  - Fatty Acids, Nonesterified/blood
MH  - Food Deprivation/*physiology
MH  - Hypothalamic Area, Lateral/anatomy & histology/*metabolism/*physiology
MH  - Injections, Intraventricular
MH  - Ketone Bodies/metabolism
MH  - Male
MH  - Neuropeptide Y/administration & dosage/pharmacology
MH  - Niacin/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Self Stimulation/*physiology
MH  - Signal Transduction/*physiology
EDAT- 1998/09/25 00:00
MHDA- 1998/09/25 00:01
CRDT- 1998/09/25 00:00
PHST- 1998/09/25 00:00 [pubmed]
PHST- 1998/09/25 00:01 [medline]
PHST- 1998/09/25 00:00 [entrez]
AID - S0031-9384(98)00050-X [pii]
AID - 10.1016/s0031-9384(98)00050-x [doi]
PST - ppublish
SO  - Physiol Behav. 1998 Jun 1;64(3):251-60. doi: 10.1016/s0031-9384(98)00050-x.