Date of Award

1974

Degree Type

Dissertation

Degree Name

Doctor of Pharmacy (PharmD)

First Advisor

Harbans Lal

Abstract

Since many drugs which are abused by man are taken orally, it was desirable to develop a method suitable to quantitatively and reliably measure oral self-administration of drugs and their effects on behavior in experimental animals. Water deprived rats were trained to lick for drug solutions (4.34 ul/lick) and bar press for food on a Fixed Interval (FI) 60 second schedule and press another bar for secondary reinforcements on a Fixed Ratio (FR)-5 schedule as three concurrent operants. Non-discriminated responding was inconsequential. An appropriate drug solution was substituted for water or the drugs were injected intraperitoneally before the session. For each drug, a dose-response was determined with usually six replicate sessions per dose for each rat. Three rats were usually used in each study. Substitution of solutions of amphetamine (0.5, 0.99 and 1.99 m Molar) resulted in concentration dependent decreases in discriminated and non-discriminated licking, and discriminated lever pressing for secondary reinforcement. Non-discriminated lever pressing for secondary reinforcement or food pellets increased. Consequential lever pressing for food pellets was unaffected. The effects of amphetamine on lever pressing and licking were similar whether an acute injection was made before the session or amphetamine was self-ingested during the session. Chronic injections of amphetamine (5 mg/kg, I.P., 18 hours before the water session, given daily for 5 days prior to the study and during the study for 30 days) resulted in an increased sensitivity to ingested amphetamine. This increased sensitivity was manifested by a shift of concentration response curves to lower concentrations l0.125, 0.25, 0.50m Molar). Chlorpromazine (0.5 mg/kg, I.P., 30 minutes before the session) significantly increased the lickin9 rates for solutions of amphetamine (0.5 mM or 1.0 mM). Substitution of solutions of ethanol (10, 20, 40, 80% v/v) resulted in concentration dependent decreased in discriminated and nondiscriminated licking, and discriminated lever pressing for secondary reinforcement. Non-discriminated lever pressing for secondary reinforcement or food pellets was increased. Consequential lever pressing for food pellets was unaffected. While the licking rate decreased with increased concentrations of ethanol, the grams of absolute ethanol ingested increased. The effects of oral injections of ethanol (12 ml/kg, of a 50% v/y solution, 15 minutes before the session on behavior were similar to the effects of ingested ethanol except for a decrease in number of food pellets obtained. Disulfiram (50 mg/kg, I.P., 60 minutes before the ethanol session) did not affect behaviors for various contingencies during water sessions or initial portions of ethanol (20% v/v) sessions. However, disulfiram pretreatment depressed behaviors completely after the initial ingestion of small quantities of ethanol. Rats were given increasing doses of morphine sulfate, until a total daily dose of 200 mg/kg was attained. Deprivation of these rats of their daily morphine for four successive days had little effect on water licking, but licking rates for a solution of amphetamine (0.5 m Molar) decreased dur1ng the abstinence while licking rates for a solution of ethanol (80% v/v) remained consistently higher than those for amphetamine. Nalorphine (4 mg/k) abolished licking for water in three of four rats. indicating a difference between nalorphine induced and abstinence induced withdrawal.

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