A pre-clinical study showing how dopaminergic drugs administered during pre-exposure can impair or facilitate latent inhibition

Abstract

Rationale

It has been suggested that, in classical conditioning, dopamine (DA) codes for (a) attention to the conditioned stimulus (CS) or (b) the intensity of the unconditioned stimulus.

Objectives

To clarify the role of DA in pre-clinical classical conditioning studies.

Methods

An existing model of classical conditioning presented by Schmajuk, Lam, and Gray (J Exp Psychol Anim Behav Process 22:321–349, 1996) suggests that DA cells in the ventral midbrain area code for the attentionally modulated internal representation of the CS. It is assumed that this representation is increased by dopaminergic agonists and decreased by dopaminergic antagonists. Computer simulations with the model describe the effect of nicotine and haloperidol on latent inhibition.

Results

Simulations replicate experimental results demonstrating that both nicotine and haloperidol affect latent inhibition when administered during the pre-exposure phase. In addition, the model reproduces data showing that administration of nicotine or haloperidol results in the impairment or facilitation of latent inhibition depending on the duration of CS or the number of CSs.

Conclusions

The model demonstrates that pre-clinical experimental results, including cell activity and pharmacological data, are consistent with an attentional role for DA in classical conditioning.

Appendices

Appendix 1: parameter values

Parameter values used in all behavioral simulations are K₁=0.2, K₂=2, K₃=0.4, K₄=0.1, K₅=0.02, K₆=0.005, K₇=0.005, K₈=0.005, K₉=0.75, K₁₀=0.3, and K₁₁=0.15. All the values are identical to those used by Schmajuk et al. (1998). With exception of K₁₀=0.3, all the values are also identical to those used by Schmajuk et al. (1996), Buhusi et al. (1999), and Schmajuk et al. (2001) who used K₁₀=0.7. Schmajuk et al. (1996) showed that simulation results are very robust for a large range of parameter values.

In the case of nicotine or amphetamine, K_DOPA=1.5. In the case of haloperidol, K_DOPA=0.5 or 0.8. Notice that while, in the case of an agonist, increasing doses are expressed as increasing K_DOPA values, in the case of an antagonist, increasing doses are expressed as decreasing K_DOPA values. The same value of K_DOPA was used in the simulations of the Joseph et al. and the Rochford et al. experiments.

Appendix 2: suppression ratios

Suppression ratios were calculated with the equation A/A+B, where A represents responding during the CS period and B represents responding during the preceding non-CS period of equal duration. We assume that responding during the CS period is given by B–CR; therefore, the suppression ratio was calculated by $B - {\text{CR}}/B - {\text{CR}} + B = B - {\text{CR}}/2B - {\text{CR}}$. The value of B, proportional to the intensity of the appetitive behavior, ranges between 0.32 and 0.53, as indicated in each figure.

Appendix 3: statistical significance

In order to estimate how well the simulated results describe the experimental data, we used a correlation test (McCall 1970). Significance level was P<0.05.