CLASSICAL CONDITIONING OF D-AMPHETAMINE- AND APOMORPHINE-INDUCED BEHAVIOR IN THE RAT

Abstract

Conditioned stereotypy and the role of dopamine in the expression of this conditioned behavior, are for the first time examined in this thesis.;In order to study the possibility that d-amphetamine (AMP) and/or apomorphine (APO) induced stereotypy and hyperactivity could be classically conditioned, male Long-Evans hooded rats (conditioned group) received 10 daily training trials of tone paired with intraperitoneal (i.p.) drug injection (one of three doses of AMP or APO). Control rats (a group for each drug dose examined) were pseudo-conditioned during the 10 training trials by pairing injection of vehicle with the tone and novel cage placement, with the appropriate drug dose being injected i.p. 15 min to 1 hr following the return of each rat to its home cage (the conditioned rats conversely received a vehicle injection at this time). On the test-for-conditioning trial (the day following the 10 daily training trials) all rats were given a vehicle injection paired with the tone and novel cage placement. Behavioral differences on this day between experimental (conditioned) and control (pseudo-conditioned) groups were examined for evidence of conditioning. The involvement of dopamine (DA) in the mediation of the postulated conditioned response (CR) was examined pharmacologically and biochemically. The ability of 0.2 mg/kg haloperidol (HAL) to attenuate the behavior of previously conditioned rats and their controls (the AMP 2.6 mg free base/kg groups) during a test-for-conditioning trial was evaluated for specificity. To examine the association of altered DA turnover with the CR, homovanillic acid (HVA) concentrations in the caudate and mesolimbic areas of conditioned rats (AMP 2.6 mg free base/kg; APO 2.5 mg/kg) and their controls (sacrificed at 30 min following the tone-vehicle pairing) were quantified fluorometrically.;The chronic effects of AMP, as determined by behavioral analysis of the conditioned groups over the 10 daily training trials, consisted of significant tolerance to AMP-induced increased activity and potentiation of AMP-induced stereotypy over trials. APO-induced hyperactivity and stereotypy showed no significant changes over the 10 daily training trials. These chronic drug results confirm the findings of previous studies.;Findings which have not been reported previously include the following: For the AMP groups, increases of head-bobbing, sniffing, horizontal locomotor activity and rearing (duration and frequency) were clearly conditioned. For the APO groups, head-bobbing and sniffing showed conditioned increases. APO proved to be a weaker stimulus for conditioning since the pooling of all the APO dosage groups was necessary to demonstrate significant conditioning of fewer behaviors.;Specific HAL-blockade of conditioned head-bobbing and sniffing without significant effects on these behaviors in the pseudo-conditioned controls was demonstrated, suggesting a specific role for DA in the mediation of these components of the CR. In addition, mean {lcub}HVA{rcub} was significantly higher in both the mesolimbic and caudate regions of the conditioned rats as compared to their pseudo-conditioned controls. These biochemical results further support the hypothesis that the demonstrated behavioral CR is mediated by dopamine. The possible involvement of other neurotransmitter systems was not specifically examined.