Ethopharmacology

There does seem to be a steady convergence of the topics of emotionality, memory, reward, feelings, etc. in the literature of the last 5 years. In the field of Ethopharmacology I see problems when attempts are made to interpret social interactions as markers of anxiety in response to anxiolytics.

Hedony is a subject which comes with its own philosopher, Epicurus, and a fine sense of struggle against the nasty Stoics and Right wing Christians who deny and despise the notion of reward or pleasure for reasons which always are revealed as ruling class fear that ordinary folk might want some joy in life!

Resting contentment seems to have two components. A basic feeling of reward just from being. Plus a resting level of security which is absolutely critical for sleep and recuperation. To give the minds of my students the flavour of a homeostasis of pleasure/reward/joy/whatever I invite them to see emotional balance or resting contentment as a floating bobbin in an oxygen meter. The updraft of gas is balanced by the pull down of gravity. Satiety is the governor that prevents reward from going off scale. The natural body under normal stimulus maintains the necessary equilibrium. Gross over indulgence blunts and destroys pleasure and the artificial violence of certain drugs burns out the mechanisms of restraint.

Perhaps the most important issue in Behavioural Studies is the power of associative stimuli to control, evoke and switch off reward chemistry. The checks and balances of resting contentment and its tidal surge in appropriate circumstances seem to share centres and circuits as if God or the Creative evolutionary process was a very parsimonious electrician who would not put in extra l or dedicated lines if the shared or party lines could suffice. Consequently the experience of such emotions as fear, frustration, revulsion, love, bonding and craving seems to be tightly interlaced in the "extended amygdala".

From the great body of work on addiction we can draw insight into the understanding of animal well being. Such papers as "Drug Abuse: Hedonic Homeostatic Dysregulation" (G. F. Koob and M. Le Moal, Science, 278, 3 Oct 1997) would reward anyone interested. What emerges from this type of study are the propositions that addiction, craving, need, affective withdrawal, depression and despair are "feelings" which animals share with us. Furthermore,"...dysregulation of hedonic homeostasis can also occur with compulsive use of non-drug reinforcers. Similar patterns of spiralling distress-addiction cycles have been observed with pathological gambling, compulsive exercise, compulsive sex, and others..."

It is not difficult for a veterinary behaviourist or ethologist to see the animal counterparts. The diagnosis and treatment of stereotypies, separation distress, and frustrative rage could be inspired and illuminated by such study.

I have S.J Cooper and C.A. Hendrie (1994), Eds., "Ethology and Psychopharmacology," NY:Wylie, at my elbow and in spare moments am sifting through the experiments described in the 18 chapters. It is evident that this painstaking and 'not a bit soft' branch of Ethology needs to do it all again!

The effects of anxiolytics on hedonic regulation as inhibitors of reward or enhancers of frustrative vigour, and the effects of serenics or antidepressive agents on both motivation and demotivation tend to have protean and unsuspected effects on the results and interpretations.

The reward from this demanding bed side reading is not insomnia but as sense of contentment as the peculiar cases of the day begin to make sense.

For example, I heard yesterday of the two Jack Russell bitches which fight savagely when one attempts to leave the room with their joint male owner and the Valium therapy which for two weeks seemed to work and then made everything much worse. I have invited the veterinarian who called in with the case to review everything and discuss with the owners the proposition that the case is (a) a typical bitch dispute about breeding rights (population density stat etc etc) and (b) the response of the aggressor bitch to valium might be explained in the context of hedonic regulation.

Thus: Valium (diazepam) is useful for the control of violent mental patients and the tempering of acute psychosis in withdrawal from various drugs. However it is susceptible to liver clearance and metabolic breakdown by conjugation as is a host of drugs (notably phenobarbitone). Activation of liver (microsomal) enzymes means that after a time the patient is effectively on a lower dose of diazepam than at the outset.

Low dosing with diazepam has accrued to itself some aphoristic tags. 1. Never give diazepam (or anxiolytics) to cases of fear aggression 2. Low dose anxiolytics will reveal repressed behaviours. 3. Women on chronic low dose Valium regimes may batter their babies because they are disinhibited from being moral.....so lock them up! (All this appeals to the moral tyrant in us and is horribly plausible.)

Something in my remote (and I am convinced) Viking genes growls "hadawayanshite" which is Old Norse for "I think these data may bear an alternative interpretation." We have found (eurekame) that dogs on low doses of anxiolytic (for noise phobia) behave in an identical way to the separated dogs studied by Panksepp and treated with naloxone. In short, agents agonistic at GABA receptors inhibit dopamine release. Agents which block opioid actions prevent disinhibition of the GABA inhibition. Thus the chemical expression of hedony (reward) is reduced or prevented. The sensation that this produces might be described as dysphoria, anhedonia, withdrawal symptoms or just plain frustration.

The failure to achieve an expected reward can result in either more vigorous attempts to chieve the reward or a deepening of misery. According to the "temperament" or "breeding" of the sufferer the results may be as follows:

The Retriever who does not get to retrieve may suddenly fly at its owner after being on anxiolytics for a time.

Panksepp's dogs resorted to face licking and attempts to solicit contact when given naloxone.

My dogs given phenobarbitone are often reported as becoming nuisances; "always underfoot", "pestering for attention", "much more affectionate" and so forth.

A depressed mother with a bawling, fractious infant, a ditto husband if he is there at all, a lousy income and horrid surroundings etc. etc. may have her "hedonic experience" even further lowered. She may smack the baby !

And of course this can all be tested by non-drug methods of inducing frustration and depression. My wife's Border terrier "Pip" pissed in the toaster because I didn't take him out enough when my wife was away. His wife (Pickles) just was plain depressed and defecated on the back door mat. Inducing conditioned behavioural inhibition in a dog by means of hiding titbits and or with sound training discs can induce acute angry frustration in a suitable dog.

I must go and make a House Call!,

Adieu,

Robin

• Another Truth by James Brody, 4/10/98
• Interaction of Medications and Social Experience by James Brody, 4/10/98