Neurochemical Correlates of Behavior. V. Differential Effects of Drugs on Approach and Avoidance Behavior in Rats with Related Changes in Brain Serotonin and Norepinephrine

Abstract

For some time it has been known that the effect of an injected drug or normal metabolite on the quantitatively measured behavior of an experimental animal depends upon a number of factors, but mainly on the drug dose, as well as on the behavioral schedule or task [1, 2]. In addition, many psychopharmacological studies that have been published contain detailed biochemical explanations of proposed mechanisms based on data obtained from nonbehavioral or “unrelated” experiments. Few studies have contained both behavioral and biochemical data on the same experimental animal, and these usually involve data from a single behavioral schedule, such as did our most recent study [3]. Measurements of two or more neurohumoral agents in different brain areas (rather than in the whole brain) from experimental animals working in two or more behavioral situations known to be differentially disrupted by either the injection of a transmitter precursor or drugs should provide useful information for the neurobiologist interested in behavior. With such data, it may be possible to correlate behavioral changes with the neurochemical changes, as has already been done in our laboratory with the single behavioral situation [3, 4, 5]. Furthermore, such data could provide a basis for determining whether a specific biochemical system (i.e., serotonergic, noradrenergic, etc.) is involved in the specific production of the behavioral response (Le., approach, avoidance, etc.). We therefore decided to study the effect of 5-HTP, p-chloroamphetamine, and tetrabenazine on approach (VR40) and avoidance (SS₂₀;RS₄₀) schedules of reinforcement and then to measure 5-HT and NE in the rat telencephalon and brain stem. DA was also measured in the telencephalon of some animals in the tetrabenazine series. The choice of these three compounds for administration to rats was based on the following data: 5-HTP, a normal metabolite and serotonin precursor, affects behavior which can be quantitatively measured [6] and is known to increase 5-HT levels in the brain without causing behaviorally related changes in NE [3, 7, 8]; DA changes in the brain stem may be related to behavioral changes, and additional studies are indicated [8]; p-chloroamphetamine also causes behavioral changes [9] and has been reported to decrease brain 5-HT levels without markedly affecting NE brain levels [10]; tetrabenazine causes behavioral changes [11] and has been reported to lower both 5-HT and brain levels [12, 13].