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How the Brain Works and More

David Longley David at longley.demon.co.uk
Tue Apr 30 06:13:00 EST 1996

The following was a 10 minute presentation with slides,  covering 
nearly  2 years work. Rules of the BPS dictate that authors  must 
be   specified   in   alphabetical   order,   with   the   senior 
author/presenter asterisked. The abstract is phrased as it is  as 
it  was  for  a pharmacology audience.  Reference to  saline,  is 
isotonic saline, ie the vehicle which naloxone was dissolved  in. 
Further  studies, delivered naloxone  intra-cerebro-ventricularly 
to  confirm  that  it  was a CNS  phenomenon.  As  a  behavioural 
experiment, the results are very clear.

In the NIMR annual report, the work was summarised as  indicating 
that endogenous opioid peptides are involved in the processing of 
novel  stimuli.  Rather  than  regard  naloxone  as   'enhancing' 
neophobia it is better to take the complement of that notion  and 
say that it retards the decline of neophobia. That decline is,  I 
have argued, co-extensive with learning, or habit formation.  The 
pre-requisite  to learning, or if you prefer, the  constraint  on 
learning,  is a variant of the UCR of neophobia. Opioids must  be 
initially OFF  (theoretical elaboration on  that point takes  one
back to a neo-Hullian model of learning/habit formation).

I have not seen anything in the literature  since this  was first
reported, and by behavioural experiment standards, it is SEEMS  a
dramatic effect. Has anyone the time, and resources to try to rep
licate the work?  The findings stand  for PVG and  Sprague-Dawley
rats, male and female.  

(introduced by T.J. Crow)

National Institute for Medical Research,
Mill Hill, London, NW7 1AA

Several   studies  report  that  naloxone,  an  opiate   receptor 
antagonist,  reduces  deprivation induced  eating  and  drinking. 
However,  in  the present study, naloxone (5mg/kg,i.p.)  did  not 
reduce food intake of rats maintained on a 22 h deprivation - 2 h
feeding   schedule.   In  contrast,   naloxone   (5   mg/kg,i.p.) 
progressively reduced water intake in deprived animals to 46%  of 
saline  treated controls. No effects of naloxone (1, 5 mg/kg)  on 
established  bar  pressing for food or water were  observed  with 
either  continuous  or fixed ratio  schedules  of  reinforcement. 
However,  naloxone (5mg/kg) accelerated extinction of  responding 
when food and water were no longer available.

Animals  treated  with naloxone (5mg/kg) during training  of  the 
bar-pressing  ate  only  26% of  the  pellets  delivered  whereas 
controls  ate  all pellets delivered. Since the animals  had  not 
previously experienced the pellets or the operant apparatus,  the
possibilities  arose that naloxone effects were due  to  enhanced 
neophobic  effects of the novel food pellets or  novel  apparatus 
cues, or were due to conditioned taste aversion. Therefore,  food 
novelty,   apparatus  novelty  and  timing  of  injections   were 
independently  varied  in different groups of 8-10  rats  treated 
with saline or naloxone. Rats were maintained at 85% body  weight 
with 12g lab chow per day. On experimental days 46 small  pellets 
(Cambden  instruments) were placed on a small petri dish  in  the 
home  cage of some groups or released from a pellet dispenser  in 
an  operant box for other groups. The dependent variable was  the 
number of pellets eaten over 15 minutes.

Naloxone (1,5 mg/kg i.p.) injected 5 or 20 min before test almost 
completely  suppressed pellet eating if the animals had not  been 
previously  exposed  to the pellets (p<0.01 't'  test  vs  saline 
groups).  This  occurred  independently  of  whether  tests  were 
carried  out  in  the home cage or novel  operant  box.  Naloxone 
induced  suppression  of  pellet  eating  was  almost  completely 
abolished  in either environment if animals had been  exposed  to 
the pellets for the five preceding days in the same or  different 
environment.  Naloxone  (5mg/kg, i.p.)  administered  immediately 
after  pellet eating tests failed to suppress  subsequent  pellet 

Thus, naloxone suppressed pellet eating if the pellets were novel 
and if naloxone was administered before eating tests. The results 
suggest  naloxone enhances neophobic effects of novel  foods  and 
that  suppression of novel pellet eating is not due  to  enhanced 
effects  of  novelty of apparatus cues or  to  conditioned  taste 


FRENK, H & ROGERS G.H. (1979) The suppressant effects of naloxone 
                              on food and water intake in the rat.
                              Behav. Neural. Biol, 26, 23-40.

1-3 April 1981
(Also British J Pharmacology 1981)
I  am  hyothesizing  a critical role for  the  endogenous  opipid 
peptides in regulating what Pavlov called "Protective Inhibition" 
or "transmarginal inhibition of intensity". Hull made much use of 
these notions in the context of Stimulus Intensity Dynamism. 

I  plan to submit the work as a full paper, as it is, apart  from 
the above brief report, the main part of a 1980s PhD thesis.

David Longley

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